UTSW researchers take new approach to fight viral infections – UT Southwestern

An immunofluorescence micrograph of cells infected by RSV (RSV is green, cells are red)

DALLAS Jan. 24, 2022 A new approach that targets the cellular machinery that viruses need to reproduce rather than the virus itself appears to stem replication of a common childhood pathogen known as respiratory syncytial virus (RSV), UT Southwestern researchers report in a new study. The findings, published in Scientific Reports, could offer a novel strategy to fight this virus and others, including SARS-CoV-2, the virus responsible for the ongoing COVID-19 pandemic.

Jeffrey Kahn, M.D., Ph.D.

RSV is far and away the major respiratory pathogen in infants and children, said study leader Jeffrey Kahn, M.D., Ph.D., Professor of Pediatrics and Microbiology, Chief of the Division of Pediatric Infectious Disease at UT Southwestern, and Director of Infectious Diseases and Medical Director of Research at Childrens Medical Center Dallas. The approach weve discovered turns the tables on this virus and potentially others in a whole new way.

RSV is a leading cause of pediatric deaths worldwide, killing an estimated 160,000 children each year, according to the National Institute of Allergy and Infectious Diseases. But although 65 years have passed since its discovery, there are still no effective treatments or a vaccine. Although some promising antiviral drugs have been explored that target components of this and other viruses, explained Dr. Kahn, viruses inevitably evolve to develop resistance against these compounds.

Taking a completely new approach, Dr. Kahn and his colleagues used genetic and pharmacological inhibition to search for vulnerable cellular pathways that RSV hijacks to replicate itself. Their experiments showed that inhibiting various components of a protein network known as the mechanistic target of rapamycin (mTOR) pathway prevented RSV from replicating in human cells. They also showed that this same strategy inhibited OC43, a human coronavirus in the same viral subfamily as SARS-CoV-2.

Because some of the drugs shown to inhibit mTOR components and block viral replication in this study are already approved by the Food and Drug Administration, they could offer hope for quick approval as antivirals against RSV, SARS-CoV-2, and other viral infections if further research confirms their utility, Dr. Kahn said.

Dr. Kahn holds the Sarah M. and Charles E. Seay Chair in Pediatric Infectious Diseases.

Other scientists who contributed to this study include HoangDinh Huynh and Ruth Levitz of UTSW, and Rong Huang of Childrens Medical Center.

This research was funded by UTSWs Department of Pediatrics and the Sarah M. and Charles E. Seay Chair in Pediatric Infectious Diseases.

About UTSouthwestern Medical Center

UTSouthwestern, one of the nations premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty has received six Nobel Prizes and includes 25 members of the National Academy of Sciences, 16 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UTSouthwestern physicians provide care in about 80 specialties to more than 117,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 3 million outpatient visits a year.

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UTSW researchers take new approach to fight viral infections - UT Southwestern

Promising ALS therapy moves closer to clinic – EurekAlert

NEW YORK, NY (Jan. 24, 2022)--An experimental drug, first tried at Columbia University Irving Medical Center as a last-ditch effort to help a 25-year-old woman withjuvenile ALS, is now being tested in ALS patients in a global, phase 3 clinical trial, based on promising results from a new study at Columbia.

The study found that the druginformally named jacifusenlowered levels of FUS, a toxic protein in the womans neurons and in mice with the disease.

The clinical trial will be pivotal in determining if the drug can slow the progression of the disease.

Though the drug was possibly too little, too late, to help the young woman who first received it, the study found that it had a profound effect, virtually eliminating the toxic proteins in the central nervous system and reducing the burden of FUS pathology dramatically, says study leader Neil Shneider, MD, PhD, the Claire Tow Associate Professor of Motor Neuron Disorders in the Department of Neurology and director of the Eleanor and Lou Gehrig ALS Center at Columbia University Vagelos College of Physicians and Surgeons.

Together with our animal data, this study suggests that the drug has the potential to delay or prevent ALS caused by mutant FUS before symptoms appear or slow clinical progression after disease onset.

The story of Jacifusen

Jacifusen gets its name from Jaci Hermstad, the first person to receive the drug, but it was already in development before Jaci was diagnosed with ALS.

ALS is usually associated with adults, but a rare and aggressive form of the disease can affect individuals, like Jaci, in their teens or 20s. The disease attacks the patients motor neurons, which control the bodys muscles, until the patient can no longer move or breathe unassisted.

Several years ago, researchers discovered that most adolescents and young adults with ALS have mutations in a gene calledFUS.

In a study of a series of mouse models with ALS-relatedFUSmutations published in 2016, and in another series in the current study, Shneider found that the mutant FUS protein is toxic to motor neurons, suggesting that lowering FUS levels by silencing the gene that makes the protein might protect neurons in ALS patients with the mutation.

In 2018, Shneider met Jaci, a young woman from Iowa whose identical twin sister had died of ALS caused by a genetic mutation in theFUSgene.Soon after, Jaci began to show signs and symptoms of ALS. Shneider immediately reached out to Ionis Pharmaceuticalsa leading developer of antisense therapeuticslooking for a drug that shuts down production of the FUS protein, which might slow the progression of Jacis disease. This led to the identification of ION363, a compound that effectively lowered FUS levels in the mouse brain and spinal cord and prevented disease onset in the mouse model of FUS-related ALS. However, this drughad never been tested in humans.

With remarkable speed, Shneider won special permission from the Food and Drug Administration to give the drug to Jaci through its compassionate use program, which makes experimental treatments available to seriously ill patients outside of clinical trials. There was no time to waste. People with these mutations usually die within a year of diagnosis, Shneider says.

Jaci received the first of several doses of the drug in 2019. We saw a significant slowdown in her functional decline, suggesting that the drug was working as intended, but sadly, her disease was already advanced by the time she began the treatment and she died about a year later, Shneider says.

New study suggests jacifusen eliminates toxic proteins

In his new study, published Jan. 24, 2022, in Nature Medicine, Shneider found that a single infusion of jacifusen at birth in a mouse model effectively silenced theFUSgene, reduced FUS protein levels in the brain and spinal cord, and delayed motor neuron degeneration in the miceall with no apparent side effects.

In Jaci, jacifusen also caused profound changes in the brain. Examination of Jacis brain tissue, donated by Jaci and the Hermstad family, found that treatment with the eponymous drug markedly reduced FUS protein clumpsa hallmark of the diseasein her brain cells. At a cellular level, jacifusen was extremely effective at doing what we hoped it would do, he said.

The findings, along with encouraging signs from 10 other patients who received jacifusen under the compassionate use program, convinced Ionis to sponsor a pivotalphase 3 clinical trialatColumbia and multiple other sites in the United States, Europe and Asia. The trial, led by Shneider, will enroll at least 64 patients.

This trial will determine if jacifusen is safe, and if it can effectively slow disease progression in symptomatic FUS-ALS patients.If approved, jacifusen would be the first treatment for this highly aggressive form of early-onset ALS, Shneider says.

Future studies will determine if jacifusen works if given to people with ALS-associated FUS mutationsbeforethey become symptomatic, as it did in the mouse studies.

This study is an example of truly personalized medicine in the 21stcentury.

More information

The study was published online [January 24, 2022] inNature Medicine.

The study is titled, Antisense oligonucleotide silencing of FUS expression as a therapeutic approach in amyotrophic lateral sclerosis. The other contributors are:Vladislav A. Korobeynikov(CUIMC), Alexander K. Lyashchenko(CUIMC),Beatriz Blanco-Redondo(Columbia andLeipzig University, Leipzig, Germany), and Paymaan Jafar-nejad (Ionis Pharmaceuticals).

The study was supported by grants fromthe National Institute of Neurological Disorders and Stroke (R01NS106236) and the Tow Foundation. Support for the FUS ASO (ION363) expanded access program was provided by Project ALS and the ALS Association. Additional funding was provided by Nancy Perlman and Tom Klingenstein and the Judith and Jean Pape Adams Charitable Foundation.

The authors declare no competing interests.

###

Columbia University Irving Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the Vagelos College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Irving Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cuimc.columbia.edu or columbiadoctors.org.

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Antisense oligonucleotide silencing of FUS expression as a therapeutic approach in amyotrophic lateral sclerosis

24-Jan-2022

The authors declare no competing interests.

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Promising ALS therapy moves closer to clinic - EurekAlert

5 Slides We’re Discussing: Gene therapy and the promise for rare disease – State of Reform – State of Reform

Gene therapies have yielded promising results for individuals experiencing rare diseases. However, these groundbreaking therapies come with their own unique set of challenges regarding who will be able to access them, how much they will cost, and how the policymaking and scientific processes will conflict as more and more therapies undergo clinical trials.

Get the latest state-specific policy intelligence for the health care sector delivered to your inbox.

Last week, we convened a panel of experts to address these questions and discuss potential solutions in our latest 5 Slides Were Watching conversation, led by State of Reforms DJ Wilson. The panel featured Danny Seiden, president & CEO of the Arizona Chamber of Commerce and Industry, Dr. Jennifer Hodge, U.S. DMD Gene Therapy Lead at Pfizer, Dr. Rafael Fonseca, chief innovation officer at Mayo Clinic, and Dr. Sharon Hesterlee, chief research officer at the Muscular Dystrophy Association.

Hesterlee brought a slide showing the prevalence of rare diseases in Arizona, noting that 5,500 Arizonans were estimated to be living with rare genetic neuromuscular diseases that were potentially treatable with gene therapy. She highlighted that Charcot-Marie-Tooth disease and Myotonic dystrophy were the most prominent, and that both diseases currently have gene therapy treatments in preclinical development.

She emphasized that ethics need to be an important part of the conversation, and that it will be critical to educate patients and families about the treatments irreversible implications as more and more therapies begin to launch.

Its a permanent change to someone. What we see in particular with parents of a child who has a pediatric disease, they are put in a very difficult position because they have to make a decision without always understanding all of the science and all of the implications.

So I think there is a huge requirement for the physician [who does the informed consent] to be very clear, and then the parents have to decide if it doesnt work, my child cannot be redosed, my child may not be eligible for another trial I think thats been a big challenge and something that weve tried to help our community in the neuro-muscular disease space navigate.

Seiden brought a slide displaying the economic benefits that would come with the increased prevalence of gene therapies. He noted that outdated systems of payment would not be applicable to this kind of treatment, and that these therapies would allow for one-time costs as opposed to a lifetime of treatment for patients with rare diseases.

When you deal with rare diseases, you need to look at it on an annualized basis over the cost of a lifetime, because gene therapy has the potential to save money and a lot of heartache for the patients and the families involved with it Arizona is one of a handful of states that allows for value-based purchasing when it comes to Medicaid contracts With the [Arizona Health Care Cost Containment System (AHCCCS)], which is by far the largest provider, theyve recognized that you have to look at patient outcomes. Its not just about that initial upfront cost.

Hodge presented a slide illustrating the unmet needs of individuals with rare diseases and the potential impacts that gene therapies can have on these individuals. She emphasized the urgent need for innovative treatments for these diseases, as 95% of rare diseases worldwide have limited or no approved treatment options, and 80% of those rare diseases have a genetic cause. She said this makes patients with rare disease collectively one of the most underserved communities in medicine today.

She said educating every organization involved in the process of developing these therapies on the stories of real patients affected by these diseases will be critical as gene therapies move through both scientific and legislative processes.

Its really to address the underlying cause of rare diseases at the root, meaning the genetics, not the symptoms It cant be a line item in a bill, it cant be something on a piece of paper that you hear about, it has to be someone telling their story [and] thinking about the patient and what theyre going through.

You can learn so much by just sitting and talking and just hearing their story, and little things that you didnt even know affected them We need to bring that to more of the audience thats involved in making some of these decisions so they can see it as more than just a line on a piece of paper when theyre deciding something.

Fonseca showed a slide explaining some specific uses of gene therapy that could potentially provide individualized, life-saving treatment to people with red blood cell diseases, as well as preventive genetic interventions for diseases like cancer.

When you think about this approach in looking at the rare disorders, it turns out that by extrapolation, a lot of the diseases that we consider common also become more and more individualized, and therefore, theyre more and more unique. More and more, we see approaches that have to be very, very much [a] tailored design for patients

To have someone who is born with [a red-blood cell disorder] return to normal red blood cell function is just enormous. This is a worldwide problem, its a problem thats associated with pain, serious medical problems, a shorter lifespan, and great expenditures for the health system, and so [Im very excited about where were at with this].

Wilson highlighted that while few gene therapies have been officially launched in the market, many are currently in pre-clinical and clinical trials and are expected to provide promising health solutions for the future.

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5 Slides We're Discussing: Gene therapy and the promise for rare disease - State of Reform - State of Reform

Worldwide Genomic Cancer Panel and Profiling Industry to 2024 – Next Generation Sequencing Fuels a Revolution – PRNewswire

DUBLIN, Jan. 24, 2022 /PRNewswire/ -- The "Genomic Cancer Panel and Profiling Markets by Cancer, by Application, by Tissue and by Gene Type with Screening potential Market Size, Forecasting/Analysis, and Executive and Consultant Guides" report has been added to ResearchAndMarkets.com's offering.

This report provides data that analysts and planners can use. Hundreds of pages of information including a complete list of Current 2021 United States Medicare Fee Payment Schedules to help understand test pricing in detail. Forecast demand for new testing regimes or technologies. Make research investment decisions. Existing laboratories and hospitals can use the information directly to forecast and plan for clinical facilities growth.

Cancer Gene Panels and Genomic Profiling are quickly changing the diagnosis and treatment of cancers. The market is moving out of a specialized niche and going mainstream as Oncologists begin routinely using information on the hundreds of genes related to cancer. The market is exploding as physicians use all the information they can get in the battle against cancer.

While Pharmaceutical Companies see the potential to make nearly any therapy viable. The report has data on how test volumes have grown for the biggest players. Find out how this new way of understanding cancer will change cancer diagnostics forever.

Comprehensive panels, genomic profiling, high risk breast cancer panels. Learn all about how players are jockeying for position in a market that is being created from scratch. And some players are pulling way out in front and expanding globally. It is a dynamic market situation with enormous opportunity where the right diagnostic with the right support can command premium pricing. And the science is developing at the same time creating new opportunities with regularity. And the cost of sequencing continues to fall.

Key Topics Covered:

1 Market Guides1.1 Cancer Panel Market - Strategic Situation Analysis & COVID Update1.2 Large Comprehensive Cancer Panel Market - Situation Analysis1.3 Guide for Executives, Marketing, Sales and Business Development Staff1.4 Guide for Management Consultants and Investment Advisors1.5 Market Size and Shares - Large Comprehensive

2 Introduction and Market Definition2.1 What are Cancer Gene Panels and Profiling?2.2 The Sequencing Revolution2.3 Market Definition2.3.1 Revenue Market Size2.4 Methodology2.4.1 Authors2.4.2 Sources2.5 A Spending Perspective on Clinical Laboratory Testing2.5.1 An Historical Look at Clinical Testing

3 Market Overview3.1 Players in a Dynamic Market3.1.1 Academic Research Lab3.1.2 Diagnostic Test Developer3.1.3 Instrumentation Supplier3.1.4 Distributor and Reagent Supplier3.1.5 Independent Testing Lab3.1.6 Public National/regional lab3.1.7 Hospital lab3.1.8 Physician Office Labs3.1.9 Audit Body3.1.10 Certification Body3.2 Oncogenomics3.2.1 Carcinogenesis3.2.2 Chromosomes, Genes and Epigenetics3.2.2.1 Chromosomes3.2.2.2 Genes3.2.2.3 Epigenetics3.2.3 Cancer Genes3.2.4 Germline vs Somatic3.2.5 Gene Panels, Single Gene Assays and Multiplexing3.2.6 Genomic Profiling3.2.7 The Comprehensive Assay3.2.8 Changing Clinical Role3.2.9 The Cancer Screening Market Opportunity3.3 Cancer Management vs. Diagnosis3.3.1 The Role of Risk Assessment3.3.2 Diagnosis3.3.3 Managing3.3.4 Monitoring3.4 Phases of Adoption - Looking into The Future3.5 Structure of Industry Plays a Part3.5.1 Hospital Testing Share3.5.2 Economies of Scale3.5.2.1 Hospital vs. Central Lab3.5.3 Physician Office Lab's3.5.4 Physician's and POCT3.6 Currently Available Large Comprehensive Assays3.7 Pricing Profiling vs. Whole Exome (or Genome) Sequencing3.7.1 Medicare Profile Pricing3.7.2 Whole Exome Sequencing

4 Market Trends4.1 Factors Driving Growth4.1.1 Level of Care4.1.2 Companion Dx4.1.3 Immuno-oncology4.1.4 Liability4.1.5 Aging Population4.2 Factors Limiting Growth4.2.1 State of knowledge4.2.2 Genetic Blizzard4.2.3 Protocol Resistance4.2.4 Regulation and coverage4.3 Instrumentation and Automation4.3.1 Instruments Key to Market Share4.3.2 Bioinformatics Plays a Role4.4 Diagnostic Technology Development4.4.1 Next Generation Sequencing Fuels a Revolution4.4.2 Single Cell Genomics Changes the Picture4.4.3 Pharmacogenomics Blurs Diagnosis and Treatment4.4.4 CGES Testing, A Brave New World4.4.5 Biochips/Giant magneto resistance based assay

5 Cancer Panels & Profiles Recent Developments5.1 Recent Developments - Importance and How to Use This Section5.1.1 Importance of These Developments5.1.2 How to Use This Section5.2 Dante Labs Acquires Cambridge Cancer Genomics5.3 Celemics, Strand Partner on Integrated Platform for NGS Analysis5.4 Myriad Genetics Recalibrates Breast Cancer Panel for All Ancestries5.5 Burning Rock Revenues Rise5.6 Caris Life Sciences to Expand Liquid Biopsy Testing5.7 OncoDiag Announces Multiplex Test for Bladder Cancer Recurrence5.8 Intermountain and Myriad Combine Test Offering5.9 Illumina, Geneseeq to Offer Cancer Testing Kits in China5.10 Exact Sciences to Offer End-to-End Cancer Testing5.11 Guardant Health Turns to Tumor Tissue Sequencing5.12 Tempus Inks Oncology Testing Collaboration With Bayer5.13 Biocartis Collaborating With GeneproDx, Endpoint Health on Tests for Idylla Platform5.14 Wales to Routinely Screen Cancer Patients With Yourgene Elucigene Test5.15 Metastatic Cancer Markers Identified in Clinical WGS Study5.16 Stitch Bio Bets on CRISPR Tech5.17 Bayer, LifeLabs Launch Free NTRK Genetic Testing Program5.18 Foundation Medicine Liquid Biopsy Gets FDA Approval for Multiple Companion Dx5.19 Progress, Challenges in Liquid Biopsy Reimbursement5.20 Israeli Startup Curesponse Raises $6M5.21 Invitae, ArcherDX Merge to Advance Precision Oncology Offerings5.22 MD Anderson Precision Oncology Decision Support to Use Philips' Informatics Solution5.23 NeoGenomics, Lilly Oncology Partner for Thyroid Cancer Testing Program5.24 Germline Results Guides Precision Therapy in Advanced Cancer5.25 FDA Clears Cancer Genomic Profiling Kit From Personal Genome Diagnostics5.26 ArcherDX, Premier Collaborate to Evaluate Genomic Sequencing Assay for Cancers5.27 Labs Reporting Cancer Risk Mutations from Tumor Testing5.28 Users Begin Integrating Genomics Data for Clinical Decision Support5.29 Fujitsu Improves Efficiency in Cancer Genomic Medicine5.30 Thermo Fisher's automated sequencer to offer same-day, pan-cancer test results5.31 Universal Genetic Testing for All Breast Cancer Patients5.32 Exact Sciences buys Genomic Health5.33 Multi-Gene Liquid Biopsy Breast Cancer Panel5.34 Thrive to Develop Earlier Detection of Multiple Cancer Types5.35 New Gene Panel Identifies High Risk Prostate Cancer5.36 Guardant Health Liquid Biopsy Test to be Covered by EviCore5.37 Biocept Partnership Offering for Liquid Biopsy Adds Several Key Services5.38 Natera Commercializes Tumor Whole Exome Sequencing from Plasma5.39 Inivata Completes 39.8M Series B Funding Round5.40 Bio-Rad Clinical ddPCR Test, Diagnostic System Get FDA Clearance5.41 CellMax, Medigen Biotech Partner in Colorectal Cancer Clinical Trials5.42 Biodesix Acquires Integrated Diagnostics5.43 Predicine, Kintor Pharmaceuticals Partner on Clinical Trials, CDx

6 Profiles of Key Players6.1 10x Genomics, Inc6.2 Abbott Diagnostics6.3 AccuraGen Inc6.4 Adaptive Biotechnologies6.5 Aethlon Medical6.6 Agena Bioscience, Inc6.7 Agilent/Dako6.8 Anchor Dx6.9 ANGLE plc6.10 ApoCell, Inc.6.11 ArcherDx, Inc6.12 ARUP Laboratories6.13 Asuragen6.14 AVIVA Biosciences6.15 Baylor Miraca Genetics Laboratories6.16 Beckman Coulter Diagnostics6.17 Becton, Dickinson and Company6.18 BGI Genomics Co. Ltd6.19 Bioarray Genetics6.20 Biocartis6.21 Biocept, Inc6.22 Biodesix Inc6.23 BioFluidica6.24 BioGenex6.25 BioIVT6.26 Biolidics Ltd6.27 bioMerieux Diagnostics6.28 Bioneer Corporation6.29 Bio-Rad Laboratories, Inc6.30 Bio-Reference Laboratories6.31 Bio-Techne6.32 Bioview6.33 Bolidics6.34 Boreal Genomics6.35 Bristol-Myers Squibb6.36 Burning Rock6.37 Cancer Genetics6.38 Caris Molecular Diagnostics6.39 Castle Biosciences, Inc.6.40 Celemics6.41 CellMax Life6.42 Cepheid (Danaher)6.43 Charles River Laboratories6.44 Chronix Biomedical6.45 Circulogene6.46 Clinical Genomics6.47 Cynvenio6.48 Cytolumina Technologies Corp6.49 CytoTrack6.50 Datar Cancer Genetics Limited6.51 Diagnologix LLC6.52 Diasorin S.p.A6.53 Enzo Life Sciences, Inc6.54 Epic Sciences6.55 Epigenomics AG6.56 Eurofins Scientific6.57 Exact Sciences6.58 Exosome Diagnostics6.59 Exosome Sciences6.60 Fabric Genomics6.61 Fluidigm Corp6.62 Fluxion Biosciences6.63 Foundation Medicine6.64 Freenome6.65 FUJIFILM Wako Diagnostics6.66 GeneFirst Ltd.6.67 Genetron Holdings6.68 GenomOncology6.69 GILUPI Nanomedizin6.70 Grail, Inc.6.71 Guardant Health6.72 HalioDx6.73 HansaBiomed6.74 HeiScreen6.75 Helomics6.76 Horizon Discovery6.77 HTG Molecular Diagnostics6.78 iCellate6.79 Illumina6.80 Incell Dx6.81 Inivata6.82 Integrated Diagnostics6.83 Invitae Corporation6.84 Invivogen6.85 Invivoscribe6.86 Janssen Diagnostics6.87 MDNA Life SCIENCES, Inc6.88 MDx Health6.89 Menarini Silicon Biosystems6.90 Millipore Sigma6.91 Miltenyi Biotec6.92 MIODx6.93 miR Scientific6.94 Molecular MD6.95 MyCartis6.96 Myriad Genetics/Myriad RBM6.97 NantHealth, Inc.6.98 Natera6.99 NeoGenomics6.100 New Oncology6.101 NGeneBio6.102 Novogene Bioinformatics Technology Co., Ltd.6.103 Oncocyte6.104 OncoDNA6.105 Ortho Clinical Diagnostics6.106 Oxford Nanopore Technologies6.107 Panagene6.108 Perkin Elmer6.109 Personal Genome Diagnostics6.110 Personalis6.111 Precipio6.112 PrecisionMed6.113 Promega6.114 Qiagen Gmbh6.115 Rarecells SAS6.116 RareCyte6.117 Roche Molecular Diagnostics6.118 Screencell6.119 Sense Biodetection6.120 Serametrix6.121 Siemens Healthineers6.122 Silicon Biosystems6.123 simfo GmbH6.124 Singlera Genomics Inc6.125 Singulomics6.126 SkylineDx6.127 Stratos Genomics6.128 Sysmex Inostics6.129 Tempus Labs, Inc6.130 Thermo Fisher Scientific Inc6.131 Thrive Earlier Detection6.132 Todos Medical6.133 Trovagene6.134 Variantyx6.135 Volition6.136 Vortex Biosciences

7 The Global Market for Cancer Gene Panels and Profiles

8 Global Cancer Gene Panels & Profiles Markets - By Type of Cancer

9 Global Cancer Gene Panels & Profiles Markets - By Type of Application

10 Global Cancer Gene Panels & Profiles Markets - By Tissue Type

11 Global Cancer Gene Testing Markets - Germline and Somatic11.1 Global Market Somatic11.1.1 Table Somatic - by Country11.1.2 Chart - Somatic Testing Growth11.2 Global Market Germline11.2.1 Table Germline - by Country11.2.2 Chart - Germline Testing Growth

12 Potential Market Opportunity Sizes12.1 Potential Cancer Screening by Country: Lung, Breast & Colorectal12.2 Potential Cancer Screening by Country: Prostate, Other Cancer & All Cancer12.3 Potential Market Size - Cancer Diagnosis12.4 Potential Market Size - Therapy Selection

13 Appendices

For more information about this report visit https://www.researchandmarkets.com/r/qwgvdr

Media Contact:

Research and Markets Laura Wood, Senior Manager [emailprotected]

For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900

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Worldwide Genomic Cancer Panel and Profiling Industry to 2024 - Next Generation Sequencing Fuels a Revolution - PRNewswire

Genetic Research Shows Rapid Immune Response in Children Protects Them From COVID-19 – SciTechDaily

Discovery of importance of interferon response in preventing serious infection will underpin new diagnostics and therapeutics.

Fundamental differences in the immune response of adults and children can help to explain why children are much less likely to become seriously ill from SARS-CoV-2, according to new research from the Wellcome Sanger Institute, University College London, and their collaborators.

The study, published in the journal Nature, is the most comprehensive single-cell study to compare SARS-CoV-2 infection in adults and children across multiple organs. Researchers found that a stronger innate immune response in the airways of children, characterized by the rapid deployment of interferons, helped to restrict viral replication early on. In adults, a less rapid immune response meant the virus was better able to invade other parts of the body where the infection was harder to control.

As part of the Human Cell Atlas1 initiative to map every cell type in the human body, the findings will be a valuable contribution to predict personal risk from SARS-CoV-2. A nasal swab to measure the immune response in newly infected adults could be used to identify those at higher risk who may be candidates for pre-emptive monoclonal antibody treatment. Recent research has also suggested inhalation of interferons could be a viable therapy2.

The immune system that we are born with is not the same as the one we have as adults. The innate immune system of children is better able to recognize dangerous viruses or bacteria automatically, triggering nave B and T cells that can adapt to the threat. Adults have a more adaptive immune system containing a huge repertoire of memory B and T cell types, which have been trained through past exposure to respond to a particular threat3. Though the adult immune system also has an innate response, it is more active in children.

One of the key mechanisms of both immune systems is a group of proteins called interferons, which are released in the presence of viral or bacterial threats and tell nearby cells to tighten their defenses. Interferons are proteins with strong anti-viral activity and their production will typically lead to the activation of B and T cells, which kill infected cells and prevent the pathogen from spreading further.

For this study, researchers at University College London (UCL) and affiliated hospitals4 collected and processed matched airway and blood samples from 19 pediatric and 18 adult COVID-19 patients with symptoms ranging from asymptomatic to severe, as well as control samples from 41 healthy children and adults.

Single-cell sequencing of the samples was done at the Wellcome Sanger Institute to generate a dataset of 659,217 individual cells. These cells were then analyzed, revealing 59 different cell types in airways and 34 cell types in blood, including some never previously described.

Analysis showed that interferons were more strongly expressed in healthy children compared to adults, with a more rapid immune response to infection in childrens airways. This would help to restrict viral replication early on and give children an immediate advantage in preventing the virus from infecting the blood and other organs.

Because SARS-CoV-2 is a new virus, it isnt something that the adaptive immune system of adults has learned to respond to. The innate immune system of children is more flexible and better able to respond to new threats. What we see at a molecular level are high levels of interferons and a very quick immune response in children that helps to explain why they are less severely affected by COVID-19 than adults.

Dr. Masahiro Yoshida, University College London

The study also detailed how the immune system of adults, with its high numbers of killer immune cells such as B and T cells, can work against the body once SARS-CoV-2 has spread to other parts of a patient.

Compared to children, adult blood has a greater number and variety of cytotoxic immune cells, which are designed to kill infected cells to prevent an infection spreading. But it is a fine line between helping and hindering. Once the virus has spread to several areas of the body, organ damage can be caused by the immune system trying and failing to control the infection. Our study shows that not only do children respond better initially, if the virus does enter the blood the cytotoxic response is less forceful.

Dr. Marko Nikolic, University College London

Knowing exactly how and why the immune response to SARS-CoV-2 can fail to control the infection or start to harm the body provides scientists with the means to start asking why certain individuals may be at greater risk of serious illness.

These data suggest that newly diagnosed adults could be tested to check interferon levels in the airway. Higher interferon levels, similar to those found in children, would suggest a lower risk of severe disease, whereas low interferon levels would suggest higher risk. Higher risk patients could then be considered for pre-emptive treatments such as monoclonal antibodies, which are expensive and can be in limited supply.

To put it simply, the innate immune response is better at fighting COVID-19 and children have stronger innate immunity, but immunity is also a complex ballet involving many types of cells. The timing and the types of cells that are triggered will influence how an infection develops, and this will vary between individuals for all sorts of reasons in addition to age. Some of the differences we observe between children and adults may help us to think about how we gauge personal risk for adults as a way of mitigating serious illness and death.

Dr. Kerstin Meyer, Wellcome Sanger Institute

In addition, there is growing evidence of the therapeutic benefits of inhaled interferon beta 1a. Based on the study results, this should be particularly the case for patients with weak or absent interferon activation.

The results are insightful not only for addressing COVID-19, but more broadly for understanding changes in the airway and blood throughout childhood. They demonstrate the power of single-cell resolution to reveal differences in the biology of children and adults, while pointing to very different considerations when thinking about how a specific disease arises and may be treated.

Jonah Cool, Chan-Zuckerberg Initiative

Reference: Local and systemic responses to SARS-CoV-2 infection in children and adults by Masahiro Yoshida, Kaylee B. Worlock, Ni Huang, Rik G. H. Lindeboom, Colin R. Butler, Natsuhiko Kumasaka, Cecilia Dominguez Conde, Lira Mamanova, Liam Bolt, Laura Richardson, Krzysztof Polanski, Elo Madissoon, Josephine L. Barnes, Jessica Allen-Hyttinen, Eliz Kilich, Brendan C. Jones, Angus de Wilton, Anna Wilbrey-Clark, Waradon Sungnak, J. Patrick Pett, Juliane Weller, Elena Prigmore, Henry Yung, Puja Mehta, Aarash Saleh, Anita Saigal, Vivian Chu, Jonathan M. Cohen, Clare Cane, Aikaterini Iordanidou, Soichi Shibuya, Ann-Kathrin Reuschl, Ivn T. Herczeg, A. Christine Argento, Richard G. Wunderink, Sean B. Smith, Taylor A. Poor, Catherine A. Gao, Jane E. Dematte, NU SCRIPT Study Investigators, Gary Reynolds, Muzlifah Haniffa, Georgina S. Bowyer, Matthew Coates, Menna R. Clatworthy, Fernando J. Calero-Nieto, Berthold Gttgens, Christopher OCallaghan, Neil J. Sebire, Clare Jolly, Paolo de Coppi, Claire M. Smith, Alexander V. Misharin, Sam M. Janes, Sarah A. Teichmann, Marko Z. Nikolic and Kerstin B. Meyer, 22 December 2021, Nature.DOI: 10.1038/s41586-021-04345-x

This research was funded by Wellcome, the Chan Zuckerberg Initiative, Rosetrees Trust, Action Medical Research, Medical Research Council and the European Unions Horizon 2020 program.

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Genetic Research Shows Rapid Immune Response in Children Protects Them From COVID-19 - SciTechDaily

British Labs Supply the World with Genetic Information about COVID-19 – VOA Learning English

British scientists have created a fast, less costly process for genome sequencing each coronavirus case they examine.

Britain is now a world leader in COVID-19 sequencing. This helps public health officials follow the spread of new variants, develop vaccines and decide when restrictions on movement are necessary.

Researchers at the Sanger Institute in Cambridge and other laboratories in Britain have a new mission. They are sharing what they have learned with scientists around the world.

The Omicron variant now spreading in many countries shows the need for worldwide cooperation, said Ewan Harrison. He is a top researcher at Sanger.

Omicron was first found by scientists in southern Africa who quickly informed the world and gave officials time to prepare.

Since dangerous mutations of the virus can happen anywhere, scientists must continually watch its development to protect everyone, Harrison said.

We cant just kind of put a fence around an individual country or parts of the world, because thats just not going to cut it, he said.

Cambridge University Professor Sharon Peacock understood the importance of sequencing the virus early in the pandemic. She knew sequencing would be important to fighting the virus. She received British government money for a national organization of scientists, laboratories and testing centers known as the COVID-19 Genomics UK Consortium.

The consortium is now working to increase knowledge of sequencing around the world. It has built training programs for researchers in developing countries. The programs include planned online classes on information sharing and working with public health officials. The goal is to help researchers build national programs to sequence COVID-19 viruses.

There is inequity in access to sequencing worldwide, the group said, adding that it wants to end the unequal situation.

By sequencing as many cases of the virus as possible, researchers hope to identify variants of concern as quickly as possible. They can then follow their spread and give early warnings to health officials.

Britain has supplied more COVID-19 sequences to researchers around the world than any country other than the United States. It has also sequenced a bigger percentage of its cases than any large nation.

Researchers in Britain have released about 1.68 million sequences, or about 11 percent of reported cases, said GISAID. GISAID is an international organization that works for quick sharing of virus information.

Over the past two years, labs around Britain have refined the process of gathering and studying COVID-19 viruses.

This has helped cut the cost of examining each genome by 50 percent. It has also reduced the time is takes to sequence from three weeks to five days, said the research group Wellcome Sanger.

Increasing sequencing ability is like building a pipeline, said Dr. Eric Topol. He is head of innovative medicine at Scripps Research in San Diego, California. In addition to buying costly sequencing machines, countries need supplies of reactive chemicals for the machines. They also need trained people to do the work and who understand the sequences. They also need systems to share the information quickly.

Meeting those needs has been difficult for many nations, including the U.S. It is even harder for developing nations, Topol said.

Many of these low- and middle-income countries dont have the sequencing capabilities, particularly with any reasonable turnaround time, he said. So, the idea that theres a helping hand there from the Wellcome Center is terrific. We need that.

Virus samples arrive from around the country. Lab assistants carefully prepare the genetic material. It is placed into the sequencing devices that read each samples unique DNA. Scientists then examine the information and compare it with other identified genomes to follow mutations. They want to see how the virus is developing.

Because COVID-19 mutates all the time, it is important to look for new, more dangerous variants that might be resistant to vaccines, Harrison said. This information will help researchers change existing vaccines or create new ones to fight the virus.

Harrison praised South Africa for quickly informing the world about the Omicron variant. But other countries, he said, punished South Africa by restricting travel and harming its economy. All nations must be permitted to publish new variant information without fear of being punished, he said.

Im Susan Shand.

The Associated Press reported this story. Susan Shand adapted it for Learning English.

__________________________________________

genome n. the entire set of genetic instructions found in a cell

sequencing n. a process of finding out the order of the amino acids forming the genetic material of an organism

variant n. something that is different in some way from others of the same kind

mutation n. a permanent change in the genes of an organism

consortium n. a group of people or companies that agree to work together

access n. the ability to get something, enter a place or meet someone

refine v. to improve (something) by making small changes

sample n. a small amount of something that is used to give information about what it was taken from

unique adj. used to say that something or someone is unlike anything or anyone else

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British Labs Supply the World with Genetic Information about COVID-19 - VOA Learning English

Xenotransplantation and the future of medicine – Hindustan Times

Amid surging Covid-19 infections driven primarily by the Omicron variant comes news of the remarkable achievement by United States (US) surgeons who implanted a heart from a genetically modified pig into a 57-year-old recipient, David Bennett, who suffered from ventricular fibrillation (a kind of heart abnormality) and had advanced heart failure. The historic procedure performed on January 7 at the University of Maryland School of Medicine (UMSOM) is a major milestone in the field of xenotransplantation the exchange of organs among species, chiefly from pigs to humans.

According to Muhammad Mohiuddin, chief of the cardiac transplantation programme at UMSOM, Bennett urgently needed a transplant and was declared ineligible for a human organ; therefore, a decision was taken to try a xenograft from a pig. The transplant team obtained compassionate use authorisation from the US Food and Drug Administration, and the organ was made available by Revivicor, a US-based biotech company. The team already had years of experience with xenografting pig hearts into baboons with a fair degree of success and were well suited to try out the exercise in humans. In 2016, they had reported that a pig heart was kept functioning in a baboon for three years.

Xenotransplantation uses animals as a source of organs for replacement therapy in humans whose own natural organs have reached the end-stage of function. Since there is always a big gap between those needing a functioning organ (chiefly heart, kidney, liver, lungs and pancreas) and the availability of the same from humans, alternative sources of donor organs have long been an unmet need.

The most significant issue with using animals as a source of transplanted organs for humans is the spontaneous immunological rejection due to the occurrence of specific antibodies produced by the human host against certain sugars present on the surface of pig cells. These get recognised as foreign, leading to hyperacute rejection in which the recipient begins to reject the organ as soon as it is implanted.

In terms of evolution, pigs and humans are quite divergent, and the major challenges are both immunological and pathophysiological. The fundamental difference is while the human system expresses the well-known ABH blood group antigens, the pigs vascular endothelium expresses a unique protein called Galactose oligosaccharide or Gala1 or simply Gal. Humans are a natural knockout for this protein that quickly triggers anti-Gal antibodies against the transplanted organ.

In recent years, significant progress has been made to genetically modify the developing piglets, rendering their tissues and organs resistant to human immune response. The creation of Dolly the sheep as the first cloned animal in 1996 provided the much-needed stimulus to do so. In their effort to create a clinical-grade facility for raising engineered pigs, Revivicor scientists produced genetic changes in a total of 10 genes: Three in the pig and seven in humans. They successfully knocked out three genes from pigs that enable the enzymes to synthesise Gal sugars, and thus minimise the formation of anti-Gal antibodies.

Simultaneously, they engineered six genes in the human host with the aim of decreasing inflammation (two genes) and blood coagulation, thereby preventing blood vessel damage (two genes) and also silenced another two regulatory proteins that promote antibody response. The final step was something that they had learnt during baboon experimentation and this included knocking out the gene for a growth hormone that ensured that the pig organ remained matched in size with the patients chest and did not outgrow upon grafting.

Two weeks have passed and the pig heart is still functioning in Bennett, making the surgical feat a remarkable achievement. However, the question of whether we have reached the stage for regular use of pig organs for transplantation in humans is still open. More science is needed to determine which modifications are critical and perhaps inescapable. It is also not clear whether different modifications may be required for different organs. For example, could there be differences for kidney versus heart and likewise for other organs? Another major barrier with xenotransplantation is the possibility of endogenous retroviruses carried by pigs and these could create safety concerns.

The other question relates to the type and extent of immunosuppression needed for the recipient because of the possibility of excessive anti-organ-specific antibodies generated in the host. While the standard immunosuppressive regimens may or may not be effective, it would be necessary to investigate immunological tools to suppress the activity of antibody-forming B-cells and inhibit their cross-talk with helper T-cells that effectively coordinate the host immune response.

While there are several issues associated with xenotransplantation, both for the recipient and society at large, the first really successful pig-to-human heart transplant achieved through the meticulous use of the tools of genetic engineering represents a significant step forward in solving the problem of organ shortage, bringing hope to those in desperate need of a transplant.

Dr Narinder Kumar Mehra is an internationally acclaimed expert in transplant immunology and former Dean of the All India Institute of Medical Sciences, New Delhi

The views expressed are personal

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Xenotransplantation and the future of medicine - Hindustan Times

Which Drugs Will Survive Climate Change? We Investigated. – VICE

You might have to experience the end of the world sober, after all.

Thats because climate change will unleash havoc on the world of drugs. And it may be a whole lot tougher on the most mainstream stimulantsgrocery store stuff like coffee, beer and winethan on hardcore illicit narcotics like heroin, cocaine and meth.

Some of those more-powerful, more-addictive, mind-altering substances appear relatively better prepared to survive the oncoming climate crisis than the vulnerable plants responsible for producing traditionally legal recreational highs, according to a review of recent scientific studies and interviews with experts on climate and agriculture by VICE News.

Heroin, for example, is already getting a boost from climate change. One study shows that rising levels of atmospheric carbon dioxide have doubled the potency of poppies, the plant used to make the drug. Wine, by contrast, is under serious threat, as changing weather patterns and raging wildfires put celebrated vineyards in jeopardy.

All plant-based drugs, whether theyre narcotics or used for medicine, are going to change, Lewis Ziska, lead author of the poppy study and now an associate professor of environmental health sciences at Columbia Universitys Mailman School of Public Health, told VICE News. In fact, the world is changing faster than our ability to describe the changes.

Though big questions remain about how climate change will impact agriculture, and experts caution that much research remains to be done, long-term agricultural consequences are just starting to come into view.

The short version: The drug world is facing a big shake-up.

To make this easier, we put the results into an oversimplified but handy-dandy chart.

For a more detailed picture, read on.

BEER: DOUBLE THE PRICE

Get ready to pay more for brew.

Climate change might make beer twice as expensive, according to a 2018 study. In Ireland, one of the heaviest beer-drinking countries in the world, the price could triple.

Thats because the cost of a key ingredient, malted barley, could soar as global average temperatures rise and barley becomes harder to grow.

The price of a six-pack in the United States might rise by as much as $8 on average, the study found.

Pricey beer is just another way climate change will suck, tweeted Steven J. Davis, one of the authors of the study.

WINE: A HINT OF ASHTRAY

Wine is decidedly in trouble.

At least, the good stuff is: Those who savor the fine distinctions between a pinot noir and a cabernet sauvignon, or a Bordeaux and a Chateauneuf-du-pape, are going to hate the future.

The world may still be able to produce the same amount of wine as before. But the quality, taste and variety of wines will change, said Benjamin Cook, a NASA climate scientist who has studied the impact of climate change on wine-growing regions.

You can grow wine grapes almost anywhere and make wine with them. Thats why you can go to Trader Joes and get 4-buck chuck, Cook told VICE News. Wine that has these characteristics that make it famous and expensive and high value, thats where the impacts are going to potentially be very severe.

Those nuances depend on the regional mix of weather, rainfall, temperature and humidityall of which will be thrown into chaos. Warmer wine-growing regions, like Australia and California, will be particularly hard hit, Cook said.

California vineyards are especially threatened by the recent surge of climate change-linked wildfires. Grapes that escape the flames can absorb chemicals from smoke that ruin their taste, leaving the dreaded smoke taint. Some winemakers complain that smoke exposure is giving their wine an ashy finish, according to The Washington Post.

Others are reaching for solutions. Kwaw Amos, owner of New Yorks Gotham Winery, blends traditional European grapes with hardier American varieties to create hybrids with better protection against heat, fungus and early budding.

The concept of hybrids is nothing new in grape growing, Amos told VICE News. Cabernet sauvignon is a hybrid. Its just now youre thinking about the next level hybrids that were going to need given whats happening.

COFFEE: DARK TIMES

Coffee is in danger.

About half of all land now used to grow the two main species of coffee, arabica and robusta, may no longer be usable by 2050, according to one estimate. Arabica and robusta make up 99 percent of the commercial supply globally, and have a limited ability to relocate to different climates.

Another study found that six-in-ten of the known species of coffee are now under threat of extinction. Experts believe higher temperatures encourage pesky fungus growth on coffee beans. Changes in rainfall patterns may also put an added stress on the plants.

Good coffee will probably become increasingly harder to grow. And that could become a global economic issue, considering the industry employs over 125 million people, including farmers, distributors and brewers. And, like beer, coffee could also get more expensive.

U.S. consumers should expect much more expensive and lower-quality coffee because of rising temperatures, extreme rainfalls, and higher frequency of severe droughts, Titus O. Awokuse, who chairs the department of agricultural, food and resource economics at Michigan State University, recently told the LA Times.

COCAINE: FINE, THANKS

Coca, the plant responsible for cocaine, is notoriously difficult to get rid of. And that likely means it will survive pretty well compared to more-vulnerable plants.

Charles Helling, a scientist who studied the crop as a soil chemist with the U.S. Department of Agriculture, has said he thinks higher temperatures wont be harmful, and that they may just encourage the plant to grow at even higher elevations.

"Coca is kind of unique, because it's got a very heavy wax cuticle, a layer on the leaves," Helling told Scientific American. "So that tends to protect it from water loss. It's a pretty hardy shrub. It's actually a lot hardier than a typical crop plant."

Another factor in cocas favor may be genetic diversity. Plants that have been extensively cultivated in mainstream agriculture tend to become more genetically homogeneous, Ziska said. Whereas plants that have thrived in the wildnot to mention, survived sustained attempts at eradicationmay demonstrate greater genetic variability that helps them respond more flexibly to a changing environment.

Its still unclear whether coca would benefit from such an advantage.

HEROIN: AS YOU LIKE IT

Poppy plants, as noted above, have already become twice as potent in natural morphine as they were in the middle of last century, thanks to rising levels of atmospheric carbon dioxide, or C02, the gas thats principally responsible for climate change, according to one study.

That study was performed in 2008, and atmospheric C02 has only continued to rise since. Pumping even more of that gas into the air may triple morphine levels by 2050, and increase potency by a factor of 4.5 by the year 2090, according to the same study.

Ziska said the reason isnt yet completely certain. But he said one theory suggests that when a given resource becomes more prevalent in an environment, plants will tend to produce more secondary compounds that are rich in that resource, and that this dynamic explains why rising atmospheric CO2 prompts poppy plants to produce more morphine.

Poppy also has another advantage that makes the plant well-suited to a drier climate: Its particularly drought-resistant.

The poppy's hardiness has enabled growers in Afghanistan, a narcostate which provides 90% of the worlds opium, to notch record harvests over the last decade.

CANNABIS: ITS COMPLICATED

Weed will probably be okaymostly.

The plant is likely well-suited to survive a moderately hotter and drier climate, according to Olufemi Ajayi, the author of a recent study on the relative dangers posed by insect pests to cannabis in the context of climate change.

But, he cautioned, only within limits. More extreme temperatures and droughts will stunt growth, or kill plants, he said.

Another 2011 study on the impact of higher concentrations of carbon-dioxide found that the plant may be able to survive under expected harsh greenhouse effects including elevated CO2 concentration and drought conditions.

Cannabis does have an otherwise unsavory link to environmental degradation, however (as do a lot of drugs: see our previous reporting here).

Indoor growing operations have spread rapidly along with broadening legalization, and they take a lot of electricity.

One estimate states that growing one ounce of cannabis indoors can emit as much greenhouse gas as burning through a large cars entire tank of gasolineor 7 to 16 gallons.

Most U.S. cannabis is grown indoors. As the industry expands, its energy consumption is expected to rise, too. In Colorado, emissions from cannabis farms already exceed those from the states coal mining industry.

In other words, weeds relationship to global warming is complex. Even if cannabis is well-positioned to withstand a moderately warmer climate, its own energy use and outsized carbon footprint will need to be accounted for if the world ever gets serious about reducing emissions.

SYNTHETIC DRUGS: FINE

The world of synthetic, lab-based drugs will likely see hardly any impact from climate change, experts including Ziska said. This is because theyre made in a lab, not grown in a field.

This diverse galaxy of stimulantswhich includes MDMA, speed, meth, LSD, synthetic cannabinoids, mephedrone, fentanyl, carfentanyl, and many morewill be relatively unaffected because much of it is far less dependent on the growth of specific agricultural crops.

Synthetic opioids, especially, have been responsible for a tidal wave of recent overdose deaths. The U.S. Centers for Disease Control estimates that 36,000 people died from synthetic opioid overdose in the U.S. in 2019, including from fentanyl, a drug 80-to-100 times stronger than morphine.

So as you contemplate the end of the world, just remember that coffee and beer may be in ever-shorter supply and growing more expensive within a few decadesbut that the worlds supply of killer fentanyl may be just as robust as ever.

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Which Drugs Will Survive Climate Change? We Investigated. - VICE

Sema4 : The Positives (and Negatives) of Medical Testing – marketscreener.com

In its recent article, "When They Warn of Rare Disorders, These Prenatal Tests Are Usually Wrong,"The New York Times published a discussion on the performance of prenatal blood screening tests. The piece, which also looked at the potential impact of results on patients, has fueled an online debate on medical ethics and misinformation. As a patient-centered health intelligence company with deep expertise in reproductive health and medical testing, we see this as a perfect opportunity to inform our partners on population health topics to help them better understand the accuracies (and inaccuracies) of clinical testing. In this guide, we aim to educate readers about the differences between screening and diagnostic tests and, crucially, why "positive" screening results should be interpreted as "further testing is recommended" and "negative" results as "no abnormalities detected; no further testing recommended."

Screening vs. diagnostic testing

Medical tests look for answers to specific health questions. Screening tests are performed to evaluate the risk of having a disease now or in the future, while diagnostic tests are performed to pinpoint the cause of a disease process and narrow down a diagnosis. Diagnostic tests also tend to be more invasive, associated with some risk, and costly. Screening tests, on the other hand, provide a cost-effective way to identify individuals at higher risk of disease, shifting the benefit-to-risk ratio to justify diagnostic testing and invasive treatments. The goal of screening tests is early diagnosis for early intervention: they provide valuable information that can indicate when diagnostic testing is needed. After diagnostic testing, an early diagnosis can help minimize long-term adverse health outcomes and optimize potential treatment options.

Noninvasive prenatal testing, or NIPT, is a blood-based screening test for expectant mothers. It evaluates the risk of fetal anomalies caused by certain chromosomal aberrations, such as aneuploidies (extra or missing chromosomes) and microdeletions (missing portions of chromosomes). Professional medical societies like the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) recommend that all pregnant women be offered prenatal screening or diagnostic testing for common aneuploidies to provide expectant parents with information about their pregnancy's risk of a genetic condition. After informed discussions with their healthcare providers about the benefits and risks of prenatal screening, this information can help parents prepare for potential complications at birth since conditions like Patau syndrome and Edwards syndrome (trisomy 13 and 18) are usually fatal by the first year of life. Early knowledge of potential complications can enable parents to deliver at a facility equipped to deal with high-risk births and connect with specialists who can guide their child's medical care.

As with all screening tests, patients opting to undergo NIPT are evaluated in the context of a larger population, based on a pre-test probability or the disease prevalence (i.e., how often a disease is present in that specific population). For example, Edwards syndrome (or trisomy 18) is the second most common fetal aneuploidy after Down syndrome, with a prevalence of one in 5,500 live births. Therefore, one newborn in 5,500 will be expected to have the condition among affected pregnancies that make it to term without screening. However, the pre-test probability also depends on patient-specific factors like ethnic background and maternal age. As the risk of fetal aneuploidy rises with age, expectant mothers are encouraged to undergo prenatal screening to detect the potential risk of fetal genetic abnormalities.

In short, screening tests are not intended to diagnose a particular condition. Instead, they serve to better personalize a person's pre-test probability of disease and weigh the need for further invasive testing.

Evaluating test utility

Test performance is evaluated based on the ability to reliably distinguish high-risk individuals or patients with disease from healthy people. A test's sensitivity gauges how well it can detect risk or disease in people who are, in fact, at high risk or sick. We can think of test sensitivity like modern home security systems that detect unexpected entries. Screening tests will detect some level of false positive alarms (perhaps, in the case of a home security system, a visiting relative), but better to be safe than sorry. The relationship between a test's sensitivity and false negativerate (the probability that an affected person incorrectly tests 'negative' or, in this case, that an intruder is not detected) can be calculated by subtracting sensitivity from 1. Because no test is perfect, positive screening results should be followed up with diagnostic tests, which are usually more specific, to facilitate a diagnosis.

Specificity gauges how well a test identifies low-risk or unaffected people who are, in fact, truly negative. When a test result is positive, specificity helps us understand whether a positive result is likely due to that disease versus other factors. The false positive rate (the probability an unaffected person incorrectly tests positive) is calculated by subtracting specificity from 1. In an ideal world, medical tests would be both perfectly sensitive and perfectly specific so that all affected individuals reliably have positive results and all healthy individuals confidently test negative. However, adjusting one of these values will generally inversely affect the other. Think of an email spam filter: setting the filter such that all emails received are sent to the spam folder would result in a filter with 100% sensitivity but at the cost of lowering specificity to 0%, which is equivalent to a false positive rate of 100%. In this case, all vital emails would be labeled as spam. In clinical practice, we are forced to strike a balance between sensitivity and specificity.

Sensitivity and specificity help speak to the accuracy of a test. Accuracy is the ability to differentiate healthy or low-risk individuals from high-risk or sick patients. It serves to estimate the strength of association between pre-test probability and post-test probability, a person's 'updated' probability of having a disease after testing. However, even in screening tests with more than 99% sensitivity, specificity, or accuracy, "positive" or "increased risk" results only tell us that an individual falls among the true positive or false positive cases. Screening tests are tuned to have higher sensitivity to cast as broad a net as possible to capture all potentially positive events, even if it means the test has slightly lower specificity, yielding a higher false positive rate. Higher sensitivity helps to maximize the likelihood of capturing all truly positive cases. This approach contrasts with diagnostic tests that aim to diagnose or "rule out" disease with near-perfect sensitivity and specificity.

Predictive values are also highly dependent on disease prevalence (Figure 1). If a disease is highly prevalent and a person tests positive for it, a high PPV means a higher likelihood that this person truly has the disease. However, as the prevalence of a disease decreases, the PPV also decreases because we can expect more false positive results for every true positive result, even with very high sensitivity and specificity. A lower PPV also increases the NPV since, for rare diseases, we can expect more individuals who are truly negative for every false negative result.

Figure 1. PPV is dependent upon disease prevalence. For equally sensitive and specific tests, PPV decreases with decreasing disease prevalence.

Therefore, the best way to think about "positive" screening test results is to interpret the result as "further testing is recommended" and "negative" results as "no abnormalities detected; no further testing recommended."

Figure 2. Post-test risk estimate is dependent on disease prevalence. Screening tests can increase our ability to detect at-risk individuals or pregnancies beyond the pre-test risk estimation for lower prevalence diseases. Pre-test, identifying individuals at risk for a rare disease is like trying to find a needle (positive case) in a haystack (larger population). However, post-test, the pile of hay (sub-population) is much smaller, and finding the needles becomes a more manageable task.

Understanding screening test results

For rare disorders and conditions with a high disease burden, the goal is to detect as many suspected cases as possible to maximize knowledge about related health risks. Take a group of 10,000 pregnant individuals in their first trimester. In this group, suppose the prevalence of a rare disorder with a high risk of miscarriage, stillbirth, developmental disability, and poor quality of life is roughly 1% (100 out of 10,000 pregnancies). Suppose these 10,000 expectant patients undergo screening for this disorder with a 99% sensitive and 95% specific test. In this scenario, we expect 100 individuals to be truly positive. With a 1% false negative rate (1-sensitivity), 99 of these 100 individuals would correctly receive a positive result. However, one affected person would incorrectly receive a negative result. Of 9,900 unaffected pregnancies, screening would correctly identify 9,405 as true negatives, although it might incorrectly label 495 healthy pregnancies as positive. We can expect about five times as many false positives as true positives and an estimated 17% PPV despite this test's excellent sensitivity and specificity.

At first glance, the above screening test may not appear informative, but the insights gained from these results are crucial. This test has captured nearly all true positive cases at higher risk of this rare disorder. Out of 10,000 individuals with a pre-test probability of 1% of having this rare disorder, it identified a subpopulation of 594 (99 true positives plus 450 false positives) individuals as 'positive' with a 17% post-test probability (PPV). That is, the screening test identified a subpopulation that is 17-times more likely to have a severe genetic disorder than the general population that was screened. The resulting 594 "positive" individuals (5.9% of the population) are now armed with results to inform critical discussions with their healthcare providers about the need for confirmatory diagnostic testing. What is important is the degree to which a screening test reliably enriches for positive cases with respect to population prevalence, allowing for a more targeted diagnostic test in a high-risk subpopulation.

In sum, the reliability of test results depends on the test characteristics discussed above. We use screening tests, combined with an individual's medical history and population variables, to determine the risk and benefit of further testing. Medical professionals, ethicists, and society at large help determine whether screening tests with particular characteristics provide enough benefit to offset the risk of potentially more invasive but more accurate testing. These foundations help establish a screening test, such as NIPT, as a standard of care in medical practice.

Noninvasive prenatal testing (NIPT)

NIPT is one form of fetal screening in which cell-free DNA from a maternal blood sample is analyzed for potential chromosome abnormalities. These screenings can also detect microdeletion syndromes characterized by physical and intellectual impairment and a higher risk of adverse health effects. Microdeletions and aneuploidies are rare in the general population, so tests for these conditions naturally have lower PPVs. Microdeletion tests are also less sensitive than aneuploidy tests, given the rarity of microdeletions and the limitations of today's technology. Their false positive rates are higher because of this lower sensitivity. However, microdeletion tests still provide significant information from false negative rates. As these tests continue to evolve, their resolution and the trade-off between sensitivity and specificity will continue to improve.

Screening tests should always be followed up with formal diagnostic testing. Patients with positive NIPT results are encouraged to undergo diagnostic procedures like amniocentesis or chorionic villus sampling for more insight into their pregnancy's risk of a genetic condition. Because these diagnostic tests carry a small risk to the pregnancy, screening tests are essential for identifying high-risk individuals who warrant more invasive testing. In addition, we encourage all families to engage in substantiative conversations with their healthcare providers so they can be better informed of their child's health now and in the future. These conversations can help them prepare for their pregnancy and make the best-informed decisions.

Navigating NIPT with Sema4

At Sema4, we know the pregnancy journey can be a whirlwind, and we're here for you throughout that journey. We aim to provide our patients, their families, and healthcare providers with valuable information from our data-driven reproductive and generational health solutions portfolio so they can make thoughtful, well-informed decisions as partners. For patients and providers interested in genetic testing options, we offer Sema4 Elements Noninvasive Prenatal Testing, a reliable, cell-free DNA NIPT screen with more than 99% sensitivity and specificity and patient-specific PPVs. This screen can detect risk with high confidence for common aneuploidies, sex chromosome abnormalities, and microdeletions in singleton and multiple gestation pregnancies. It also detects fetal sex as early as nine weeks gestation.

Support and education are essential when undergoing NIPT. As such, Sema4 provides patients with educational materials to help them learn more about the role of genetic testing. In addition, our genetic counselors are available to offer guidance and support for patients with positive results during what can be a worrisome time. Sema4 is also heavily invested in research to advance maternal-fetal health, including predictive modeling to determine the optimal timing to receive NIPT and achieve the most accurate results.

_ _ _

For more information on Sema4 ElementsTM, our portfolio of information-driven genomic solutions, digital tools, and services that enable providers to treat patients holistically during their reproductive and generational health journey, please click here.

1) Calculated using the National Society of Genetic Counselors (NSGC) NIPT/Cell Free DNA Screening Predictive Value Calculator

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Sema4 : The Positives (and Negatives) of Medical Testing - marketscreener.com

UC Davis Health’s partnership in telegenomics improves accessibility to genetic medicine with telemedicine robots – The Aggie – The Aggie

Telemedicine robots allow for genetic consultations around the clock virtually

Now more than ever, telemedicine has been the epitome of health care since the pandemic struck. Fears surrounding the coronavirus and inconvenient commutes have made an in-person visit to the doctor unappealing. However, long before the pandemic, UC Davis Health entered a partnership with Dignity Health Mercy San Juan Medical Center in Carmichael, working together on telemedicine to enhance accessibility to all patients.

Dr. Katherine Rauen, emeritus in the Division of Genomic Medicine and a professor in the Department of Pediatrics at UC Davis Health, explained the significance of TeleGenomics and why UC Davis is at the forefront of telemedicine.

UC Davis has a really big catchment, meaning that the patients that we see go all the way up to the Oregon border, go all the way inland, and we actually have a lot of patients from Reno and Nevada, Rauen said. And our catchment goes all the way down through the central Valley. So geographically, we have a huge catchment and there are a lot of patients that the drive is very long for them; they may not have the transportation that they need to get to the UC Davis Medical Center and so telemedicine was the answer and it still is the answer.

Despite the field of genomic medicine being housed under the Department of Pediatrics, Rauen further explained why this field actually extends beyond just pediatric patients.

We transcend all age groups, so even though were housed within the Department of Pediatrics, we see newborn children to adults in their 70s or 80s, or whoever wants to come and see us, Rauen said. Genomic medicine is a family affair. And what impacts you genetically impacts other family members, it could potentially impact other family members as well. We are a product of our genes, and our genes come from the previous generation, so it makes us who we are.

The fields wide encompassing range of patients and UC Davis large catchment led to the development and usage of state-of-the-art telemedicine robots. These robots equipped with high resolution cameras allow UC Davis genetics specialists to conduct virtual yet thorough examinations for patients all the way at the Dignity Health Mercy San Juan Medical Center around the clock.

There have been several studies that have been done that show that, yes, this is a robust way to see patients because the robots have gotten so advanced that I can see freckles and moles on somebodys skin; I can see the palmar creases on the patient, Rauen said.

Many patients call in for a variety of reasons regarding a genomic medicine issue. This is where these telemedicine robots that have made healthcare accessible to patients distant from UC Davis Medical Center around the clock come in.

The consultations are requested for a variety of reasons. For example, when a child born at Methodist Hospital or Mercy San Juan has multiple congenital anomalies, such as heart or skeletal defects, isnt eating properly, or has features that are consistent with Down syndrome, according to a recent UC Davis Health press release.

Dr. Joseph Shen, a clinical geneticist trained in molecular biology and molecular genetics at the UC Davis Medical Center, described how the pandemic had affected TeleGenomics for both physicians and patients.

Some technologies can be slow to adopt or people are old school and dont want to change and things like that, but I think that [the pandemic] really accelerated it forward to use it more and more, Shen said. From a practical standpoint, when doing a genetics evaluation, we are very thorough with how were examining the body; were looking for little physical clues up and down, [which] is best served if youre doing that in person. But Ive seen run-throughs with these robot systems with the intricate amount of detail that were able to zoom in on as if we were doing these examinations in-person.

With telemedicine shaping the health field, there were inevitably doubts of how a virtual visit lacks the same effectiveness compared to an in-person visit. However, Rauen described how in the past few years, these robots have facilitated genomic consultations virtually with just as much value as in-person consultations.

We have gotten very positive feedback on [telemedicine robots], and it was just like we were right there talking with them, so it makes a huge difference to have a face-to-face interaction, and they looked at it as if it were face-to-face, Rauen said. It does feel on our end as though we were present with the family. So to me, having done this a couple of decades and looking back on it, its like I really was there at the bedside.

Written by: Brandon Nguyen science@theaggie.org

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UC Davis Health's partnership in telegenomics improves accessibility to genetic medicine with telemedicine robots - The Aggie - The Aggie

Could gene therapies be used to cure more people with HIV? – aidsmap

Medical science is starting to license and use drugs and procedures that change the genetic code inside the bodys cells, and to correct the bad code that can give rise to conditions such as cancer and the auto-immune diseases. Since HIV is a disease that results from a virus inserting such a piece of bad code into our genes, such therapies could be used to snip out that code and effect a cure.

This was what attendees at last months International AIDS Society Conference on HIV Science (IAS 2021) heard at the workshop on curing HIV. The workshop opened with two introductory talks by Professor Hans-Peter Kiem, the chair of gene therapy at the Fred Hutchinson Cancer Research Center in Seattle in the US (the Fred Hutch) and, in a joint presentation, by the Fred Hutchs Dr Jennifer Adair and Dr Cissy Kityo of the Joint Clinical Research Centre (JCRC) in Kampala, Uganda.

The latter talk was a sign of acknowledgement that, while the prospects for genetic medicine are brighter than ever before, their expense and sophistication do not fit well with the global epidemiology of HIV, which mainly affects the worlds poorest and most disadvantaged communities. Despite this, Fred Hutch and JCRC have embarked upon a joint research programme to develop within the next few years a genetic therapy treatment for HIV that could be realistically scaled up for use in lower-income settings.

A unit of heredity, that determines a specific feature of the shape of a living organism. This genetic element is a sequence of DNA (or RNA, for viruses), located in a very specific place (locus) of a chromosome.

A type of experimental treatment in which foreign genetic material (DNA or RNA) is inserted into a person's cells to prevent or fight disease.

To eliminate a disease or a condition in an individual, or to fully restore health. A cure for HIV infection is one of the ultimate long-term goals of research today. It refers to a strategy or strategies that would eliminate HIV from a persons body, or permanently control the virus and render it unable to cause disease. A sterilising cure would completely eliminate the virus. A functional cure would suppress HIV viral load, keeping it below the level of detection without the use of ART. The virus would not be eliminated from the body but would be effectively controlled and prevented from causing any illness.

The body's mechanisms for fighting infections and eradicating dysfunctional cells.

In cell biology, a structure on the surface of a cell (or inside a cell) that selectively receives and binds to a specific substance. There are many receptors. CD4 T cells are called that way because they have a protein called CD4 on their surface. Before entering (infecting) a CD4 T cell (that will become a host cell), HIV binds to the CD4 receptor and its coreceptor.

HIV cure research pioneer Dr Paula Cannon of the University of Southern California, chairing the session, said: After several decades of effort and false starts, gene therapies now hold out promise for diseases that were previously untreatable.

Hans-Peter Kiem acknowledged the pivotal role of community advocacy in supporting cure research, noting that his project, defeatHIV, was one of the first beneficiaries of a grant from the Martin Delaney Collaboratories, named after the celebrated US treatment activist who died in 2009.

The other factor that gave impetus to HIV cure research was, of course, the announcement that someone had been cured: Timothy Ray Brown, whose HIV elimination was first announced in 2008 and who came forward publicly in 2010. He died in 2019 from the leukaemia whose treatment led to his HIV cure but by then had had 13 years of post-HIV life. He had survived long enough to talk with Adam Castillejo, the second person cured of HIV, and encourage him to come forward too.

Timothy and Adams stories showed that HIV could be cured, and with a crude form of gene therapy too: cancer patients, they were both given bone marrow transplants from donors whose T-cells lacked the gene for the CCR5 receptor, which is necessary for nearly all HIV infection.

But there have only been two cures for two reasons: firstly, bone marrow transplant is itself a very risky procedure involving deleting and replacing the entire immune system of already sick patients. In 2014 Browns doctor, Gero Hutter, reported that Timothy Ray Brown was only one of out of eight patients on whom the procedure had been tried, but that all the others had died.

Secondly, compatible bone marrow donors are hard to come by as it is, and restricting them to the 1% or so of people who lack the CCR5 receptor, all of them of northern European ancestry, means very few people could benefit from this approach. Attempting transplant with T-cells that do not lack CCR5, in the hope that replacing the immune system with cells from a person without cancer will also get rid of their HIV anyway, has produced temporary periods of undetectable HIV off therapy, but the virus has always come back.

(People like Brown and Castillejo, whose HIV infection was cured by medical intervention, need to be distinguished from people who seem to have spontaneously cured themselves, such as Loreen Willenberg: such people are of course of great interest to cure researchers, but the trick is to make it happen consistently in other people.)

Brown and Castillejos cures, as transplants, were so-called allogenic, meaning that the HIV-resistant cells came from another person. Better would be autogenic transplants, in which immune system cells are taken from a person with HIV, genetically altered in the lab dish to make them resistant to HIV, and then re-introduced. This type of procedure written about for aidsmap as long ago as 2011 by treatment advocate Matt Sharp, who underwent one.

The repertoire of gene therapies is not restricted to CCR5 deletion. Gene therapy is immensely versatile, and could be used in a number of ways.

Instead of using gene therapy to make cells resistant to HIV, it could directly repair defective genes in cells by means of cut-and-paste technology such as CRISPR/Cas9. This is already being used in trials for some genetic conditions such as cystic fibrosis and sickle-cell anaemia. Given that HIV-infected cells are also defective in the sense that they contain lengths of foreign DNA that shouldnt be there, they are amenable to the same molecular editing. Early trials have produced promising results but the challenge, as it has been in a lot of gene therapy, is to ensure that the cells containing DNA are almost entirely eliminated.

One way of doing this is not to delete the HIV DNA from infected cells but to preferentially kill off the cells themselves by creating so-called chimeric antigen receptor (CAR) T-cells. These are T-lymphocytes whose genes have been modified so that their usual receptors such as CD4 or CD8 have been replaced with receptors attuned very specifically to antigens (foreign or unusual proteins) displayed by infected cells and cancer cells. A couple of CAR cell therapies are already licensed for cancers; the problem with HIV is that the reservoir cells do not display immune-stimulating antigens on their surfaces. This means that CAR T-cells would have to be used alongside drugs such as PD-1 inhibitors that stop the cells retreating into their quiescent reservoir phase, an approach demonstrated at IAS 2021.

A couple of other approaches could be used to produce either vaccines or cures. One is to engineer B-cells so they produce broadly neutralising antibodies. A way of tweaking them to do this, called germline targeting, is covered was also discussed at IAS 2021, but if we manage to generate B-cells that can do this, we could then in theory directly edit their genes to make them do the same thing.

"Timothy Ray Brown and Adam Castillejo were both given bone marrow transplants from donors whose T-cells lacked the gene for the CCR5 receptor."

The other way is to induce cells to make viral antigens or virus-like particles that the immune system then reacts to. Scientists have been working on this technique for 20 years and it triumphed last year when the Pfizer and Moderna vaccines against the SARS-CoV-2 virus had over 90% success in suppressing symptomatic COVID-19. These vaccines are not genetic engineering in the sense of altering the genome of cells; rather, they introduce a product of the genetic activation in cells, the messenger RNA that is produced when genes are read and which is sent out into the rest of the cell to tell it to make proteins.

However because HIV is more variable and less immunogenic than SARS-CoV-2, the vaccine induced by the RNA would have to be something that looked much more like a whole virus than just the bare spike protein induced by the Pfizer and Moderna vaccines. If there was such a vaccine could be used both therapeutically as well as in prevention, by stimulating an immune reaction to activated HIV-infected cells. Moderna have announced they will now resume the HIV vaccine research they were working on when COVID-19 hit.

The problem with all these more gentle procedures is that it has proved difficult to replace all the HIV-susceptible cells with the HIV-resistant or HIV-sensitised ones: although engraftment takes place, meaning that the autologous cells are not rejected by the body and are able to establish a population for some time (in some animal experiments, replacing as much as 90% of the native immune cells), eventually the unaltered immune cells tend to win out because the introduced cells lack the deep reservoir of replenishing cells.

Kiem said that the way scientists have been trying to get round this is to only select and alter so-called haematopoeic stem cells (HSCs). These rare and long-lived cells, found in the bone marrow, are the replenishing reservoir of the immune system. They differentiate when they reproduce and give rise to all the immune cells that do different things: CD4 and CD8 T-lymphocytes, B-cells that make antibodies, macrophages that engulf pathogens, dendritic cells, monocytes, natural killer cells, and others.

Altering HSCs genetically so that they are able to fight HIV in one way or another could in theory give rise to a persistent, HIV-resistant immune system. They could in theory lie in wait and be ready to produce effector cells of various types. They would be ready when a new HIV infection comes along (if used as a vaccine) or when HIV viral rebound happens and there is detectable virus in the body (if used as part of a cure). If a person with CAR-engineered stem cells could have repeated cycles of treatment interruption, their HIV reservoir could in theory slowly be deleted.

"Gene therapies are astonishingly expensive."

As mentioned above, although genetic medicine shows enormous promise, the complexity and expense of its techniques means that at present it is unlikely to benefit most people who really need it.

Hans-Peter Kiem said that currently about 60 million people have conditions that could benefit from gene therapy. The vast majority of these either have HIV (37 million) or haemoglobinopathies blood-malformation diseases such as sickle-cell anaemia and thalassaemia that are also concentrated in the lower-income world (20 million).

Dr Jennifer Adair, one of the first researchers to have proposed collaboration on gene therapies for HIV with African institutes, said that gene therapies have already been licensed for conditions such as thalassaemia, spinal muscular atrophy, T-cell lymphoma and a form of early-onset blindness.

But they are astonishingly expensive. The worlds most expensive drug tag goes, depending on which source you read, either to Zynteglo, a genetic medicine correcting malformed beta-haemoglobin and licensed in the US for thalassaemia, or Zolgensma, a drug licensed in Europe and given to children to correct the defective gene that results in spinal muscular atrophy.

Both cost about 1.8 million for a single dose. The price is not just due to the cost of the complex engineering used to make them, but because they are used to treat rare diseases and so have a small market.

At present the technology need to engineer autogenic genetically engineered cells is, if anything, even more expensive and complex than that needed to introduce allogenic cells. It can involve in the region of ten staff and a workspace of 50 square metres per patient. Recently a so-called gene therapy in a box has been made available that can reduce the area needed to produce autogenic genetically-engineered cells from 50 to less than one square metre, and the staff need to one or two, But what is really needed is genetic engineering in a shot; a therapy similar to a vector or RNA vaccine that can be introduced as an injection and produces the genetic changes needed within the body.

Undaunted by the challenges, the US National Institutes of Health are collaborating with the Bill and Melinda Gates foundation to work on a combined programme of HIV and sickle-cell-anaemia genetic therapy (given that something that works for one could be adapted to work with the other).

And the Fred Hutchinson Center has teamed up with the Joint Clinical Research Centre in Uganda with the very ambitious goal of making a genetic therapy that would be at least ready for human testing within two years in an African setting, and that could be scaled up to be economical for Africa if successful.

Dr Cissy Kityo of JCRC in Uganda told the conference that as of 2020, there were 373 trials of gene therapy products registered, of which 35 were in phase III efficacy trials. The global budget for regenerative medicine, which includes genetic therapy and related techniques, was $19.9 billion, having jumped by 30% since the previous year. The US Food and Drug Administration projects that based on the current rate of progress and the development pipeline, they may be licensing around 100 gene-therapy products a year by 2025.

This branch of medicine is no longer exotic, she said. Now steps have to be taken to trial gene therapies in the people who needed them most, and to turn the exotic into the affordable, she added.

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Could gene therapies be used to cure more people with HIV? - aidsmap

What to expect at the FDA’s two-day meeting on gene therapy safety – BioPharma Dive

Over the past several years, drugmakers have inundated the Food and Drug Administration with scores of applications to begin clinical trials of experimental gene therapies for a wide array of inherited diseases.

The wave of submissions reflects a research boom that's brought two gene therapies to market in the U.S. and numerous others into later stages of testing. Awash in funding, new gene therapy biotechs have proliferated and, with them, a pipeline that by one count now exceeds 300 would-be treatments.

Yet, while gene therapy has made huge strides since its emergence in the late 1980s, many scientific questions remain, particularly now that more and more patients are being treated in clinical trials.

To help answer some of those questions, the FDA has asked a panel of gene therapy experts to evaluate an array of safety risks to the complex and cutting-edge treatments.

The meeting, which will be held virtually Thursday and Friday, could help the agency set new guardrails for running gene therapy trials and for monitoring participants afterwards. And for a field that's advancing quickly, the discussion could serve as a reminder of the risks of treatments often characterized by their potential for dramatic benefit.

Here's what to expect:

The FDA is focusing the discussion on the safety risks presented by one of the more commonly studied types of gene therapy, namely treatments delivered by a harmless virus called adeno-associated virus, or AAV.

AAVs are a popular tool for shuttling functional copies of genes into the cells that need them. Luxturna, a blindness treatment developed by Spark Therapeutics that became the first gene therapy approved in the U.S., uses AAV, as does Zolgensma, a therapy for spinal muscular atrophy sold by Novartis. Many other gene therapies that are still in testing do as well.

Over the course of the two days, the panel will discuss the cancer risk posed by AAV gene therapy, as well as toxicity to the liver and brain that's been observed in animal testing and in humans.

FDA officials and researchers from top academic centers will present on each safety concern, after which the panel will debate how best to assess that risk and whether it can be prevented or mitigated by better treatment or study design.

The roster of speakers is headlined by Jim Wilson, a star gene therapy researcher with the University of Pennsylvania. Wilson led the gene therapy trial that resulted in the 1999 death of study volunteer Jesse Gelsinger. Since that tragedy, however, he's become a pioneer in the development of AAV vectors, forming multiple biotechs like RegenxBio and Passage Bio in the process.

But as use of AAV vectors has become more widespread and developers test higher and higher doses, Wilson has also been a voice of caution. A paper his group at UPenn published three years ago described liver and nerve damage in animal experiments, a finding his team used to call for researchers to do more monitoring. Wilson will deliver two separate presentations at the meeting, respectively focused on liver or neurological side effects in preclinical studies.

The meeting will feature talks from other gene therapy researchers and investigators as well. Ronald Crystal, the chair of genetic medicine at Weill Cornell who has worked on gene therapy since 1987, will discuss the use of AAV vectors in the brain. Lindsey George, a Children's Hospital of Philadelphia investigator involved in multiple hemophilia gene therapy trials, will talk about liver toxicity observed in human studies.

Only one industry representative, from Novartis, will present to the panel. That talk will center around three cases of a rare clotting syndrome that were observed in post-marketing surveillance of Zolgensma last year. A warning alerting doctors of the potentially serious side effect, known as thrombotic microangiopathy, is now in Zolgensma's prescribing information.

Safety concerns have dogged gene therapy ever since a series of setbacks two decades ago temporarily halted research and chilled further investment. Improved delivery tools, such as AAV, have helped address some of those concerns, and AAVs are now used in dozens of clinical trials.

But as the use of AAVswidened, more serious side effects have been reported, reviving safety questions and grabbing the attention of regulators.

The FDA cited recent research, for instance, that found roughly a third of AAV gene therapy trials had a "treatment-emergent serious adverse event."

Some of those have led to tragic results, or to significant patient concerns. In a clinical trial of an Audentes Therapeutics gene therapy for a rare neuromuscular disease, liver-related side effects lead to the death of three patients. Immune-related side effects have occurred in testing of Duchenne muscular dystrophy gene therapies from Solid Biosciences and Pfizer as well as of a vision loss treatment from Adverum Biotechnologies.

A participant in a study of a UniQure gene therapy for hemophilia, meanwhile, was diagnosed with liver cancer, though the biotech later concluded its gene therapy was "highly unlikely" to be the cause.

Worrisome findings have been found in animal tests with AAV vectors as well, which, taken together, has led to "questions about causality and risk mitigation," the FDA said.

Advisory committee meetings are just that. The FDA uses them as a sounding board for issues it's wrestling with, but it's not required to follow the advice given by the assembled experts.

In gene therapy, though, the FDA and drugmakers are both learning as they go. The agency has firmed up its thinking on a number of topics, finalizing a slate of six guidance documents early last year, but it's still developing the rules of the road.

The questions the FDA posed to its advisers cover a lot of ground and many are open-ended. But they give clues to the direction the agency is thinking.

Several of the questions ask the experts whether the FDA should set an upper limit on the size of gene therapy doses due to the risk of serious brain and liver toxicity, both of which have been associated with higher doses in several instances.

With liver toxicity, the FDA wants to know if there are patient factors other than weight that should be considered when determining a dose, a line of inquiry that could impact how clinical trials are run.

Other questions suggest the FDA is particularly interested in whether animal studies could be better designed to assess the risk of cancer or liver damage before testing in humans starts.

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What to expect at the FDA's two-day meeting on gene therapy safety - BioPharma Dive

Global DNA Sequencing Report 2021: There is a Move Toward a More Consumer-Focused Model – Yahoo Finance

DUBLIN, Sept. 3, 2021 /PRNewswire/ -- The "Global DNA Sequencing: Research, Applied and Clinical Markets" report has been added to ResearchAndMarkets.com's offering.

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The report's scope covers sequencing technologies, industries, applications, patents, initiatives and companies. The markets for sequencing services and products are given for the years 2020, 2021 and 2026.

This report reviews the leading sequencing technologies and describes why genetic variation is essential in clinical testing. It then discusses some of the important research initiatives that impact sequencing applications. The main market driving forces for sequencing services and products are listed and discussed.

The DNA sequencing industry has achieved notable growth from its beginnings to become a vital sector in the life sciences industry.

Sequencing plays a central role in many life science megatrends, including synthetic biology, precision medicine, population and consumer genomics; tissue-agnostic drugs; liquid biopsy; blockchain technologies, gene editing and a shift toward consumerism. These major trends favor rising sequencing adoption and growth in the future.

For example, in clinical diagnostics, there is a move toward a more consumer-focused model. This will propel the demand for genomics technologies as consumers will want to better understand the role that genetic variations and genes have in their future health outcomes.

Significant developments in the research space include the growth of large-scale sequencing initiatives and support for sequencing by major governmental funding agencies.

Major developments in the applied space include the proliferation of population-scale sequencing projects around the globe, the use of sequencing by biopharma for the selection of patients for clinical trials of precision medicines and an increase in synthetic biology and agriculture applications.

Population-scale sequencing projects have various positive effects on the sequencing market. These projects give insight into how genetic variation contributes to disease diagnosis, risk prediction and treatment; advance knowledge about genetic variation within and across populations; and facilitate the development of new sequencing tools and analysis methods.

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Significant developments in the clinical space include the launch and fast growth of NIPT, companion diagnostics for tissue-agnostic drugs and for drug development, and a growing installed base of sequencing instruments for genetic testing. Important clinical sequencing applications include reproductive health, oncology, rare and undiagnosed diseases, and transplant medicine.

Genomics (including sequencing) is a key medical technology. Once the human genome had been sequenced, medical researchers were able to start identifying disease-causing variations in the genetic code. Drugs could then be targeted to specific genes, offering tailored treatments.

This also opened up a market opportunity in clinical trials to select a subgroup of patients who will respond to the drug. As a result, drugs that may have failed clinical trials due to side effects among a general population could make their way through the trials with a genetically targeted subgroup.

For market estimates, data is provided for 2020 as the base year and for 2021, and it is forecast through year-end 2026. Estimated values used are based on product manufacturers' and service providers' total revenues. Projected and forecasted revenue values are in constant U.S. dollars that have not been adjusted for inflation.

Report Includes:

Analyses of the global market trends, with data from 2020, estimates for 2021, and projections of compound annual growth rates (CAGRs) through 2026

Estimation of the market size and market forecast for DNA sequencing industry, and corresponding market share analysis by delivered format, product type, end use segment, application, disease category, and geography

Highlights of key market dynamics (DROs) for DNA sequencing, regulatory scenario, and impact of COVID-19 on the progress of this market

Discussion of market opportunities for DNA sequencing, industry structure, applications and business considerations of sequencing technologies, along with ongoing dramatic changes in the structure of MedTech industry

Review of the leading next-generation sequencing (NGS) technologies, emerging applications, and penetration of DNA sequencing-based diagnostics and research initiatives affecting the marketplace

Patent analysis for novel sequencing technologies, latest developments, clinical trials, and potential markets for future developments

Insight into the sequencing industry activities including major acquisitions and strategic alliances, competitive benchmarking of key sequencing industry participants and their growth strategies

Market share analysis of the key companies of the industry and their detailed company profiles including Agilent Technologies, Becton, Dickinson and Co., Bio-Rad, Danaher Corp., Illumina Inc., Merck KGaA, Roche, and Thermo Fisher

Impact of COVID-19 Pandemic

Introduction

Impact on MedTech

Elective and Noncritical Procedures

Shift in Manufacturing

Regulatory Delays, Clinical Trials and Product Launches

Supply Chain Disruptions

Impact of COVID-19 on DNA Sequencing

Company Profiles

Admera Health

Adaptive Biotechnologies Inc.

Agilent Technologies Inc.

Ambry Genetics

Asuragen Inc.

Athena Diagnostics Inc.

Baylor Genetics

Becton, Dickinson And Co.

Berry Genomics Co. Ltd.

Bgi Shenzhen

Biodesix Inc.

Bio-Rad Laboratories Inc.

Caredx Inc.

Caris Life Sciences

Cegat Gmbh

Cellmax Life

Centogene Ag

Coopersurgical Inc.

Cygnus Biosciences Co. Ltd.

Danaher Corp.

Darui Biotechnology Co. Ltd.

Devyser Ab

Diacarta Inc.

Dna Electronics

Electronic Biosciences

Epic Sciences Inc.

Eurofins Scientific

Fry Laboratories Llc

Genapsys Inc.

Gendx Bv

Gene By Gene Ltd.

Genomatix Software Gmbh

Genome Profiling Llc

Golden Helix

Grandomics Biosciences Co. Ltd.

Guardant Health Inc.

Helix Opco Llc

Histogenetics Llc

Htg Molecular Diagnostics Inc.

Illumina Inc.

Inex Innovations Exchange Pte. Ltd.

Inivata Ltd.

Interpace Diagnostics Llc

Invivoscribe Inc.

Irepertoire Inc.

Kew Inc.

Laboratory Corp. Of America Inc.

Macrogen Inc.

Mdxhealth Inc.

Merck Kgaa

Myriad Genetics Inc.

Natera Inc.

Neogenomics Laboratories

New England Biolabs

Ngenebio Co., Ltd.

Novogene Co. Ltd.

Nugen Technologies Inc.

Omniseq Corp.

Oxford Nanopore Technologies Ltd.

Pacific Biosciences Of California Inc.

Paradigm Diagnostics Inc.

Parseq Lab Co. Ltd.

Perkinelmer Inc.

Personal Genome Diagnostics Inc.

Personalis Inc.

Predicine Inc.

Preventiongenetics Inc.

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Global DNA Sequencing Report 2021: There is a Move Toward a More Consumer-Focused Model - Yahoo Finance

Agathos Biologics Receives $900,000 from the North Dakota Bioscience Innovation Grant Program – Yahoo Finance

FARGO, N.D., August 30, 2021--(BUSINESS WIRE)--Agathos Biologics, a biotechnology company developing transformational science within a strong ethical and moral framework, today announced the company has been awarded $900,000 from the North Dakota Department of Agriculture Bioscience Innovation Grant (BIG) Program. Agriculture Commissioner Doug Goehring announced that nine grants have been awarded totaling $4.9 million to foster the growth of the bioscience industry in North Dakota. "Advances in bioscience have already transformed many sectors including agriculture and medicine," Goehring said. "These grants will help North Dakota stay on the forefront of bioscience innovation."

Agathos Biologics project funded by ND BIG will focus on challenges that limit patient access to advanced genetic medicines that can significantly impact quality of lifecost, availability, and ethical concerns. Company scientists will create new materials and methods for research and biomanufacturing and use them for drug development, which will address unmet medical needs and increase the availability of genetic medicines to more patients. The company will make these products and services available to the broader biotechnology industry through direct sales and licensing, partnerships, and collaborations.

"We are honored to receive this support from the State of North Dakota and thank the Commissioner and the Committee for their work on behalf of the citizens of the state," said James Brown, Chief Executive Officer of Agathos Biologics. "We founded the company in North Dakota because its business-friendly environment, skilled workforce, and growing biotechnology ecosystem make it an ideal place to expand the company and achieve our goal to develop genetic medicine products and services that positively impact human health and are ethically acceptable to all."

About Agathos Biologics

Agathos Biologics is a biotechnology company pursuing transformational science in biomanufacturing, biologic payload delivery, and cell and gene therapy. Discoveries in bioprocessing and genetic characterization and control have created an abundance of scientific possibilities that can help us all lead better lives. Our mission as the good science company is to create breakthrough products and services within a strong ethical and moral framework that benefits everyone. We believe in science that serves and have a relentless focus on serving our clients, employees, and society. For more information, please visit http://www.agathos.bio.

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Contacts

James BrownCEO701-415-3395james.brown@agatho.bio

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Agathos Biologics Receives $900,000 from the North Dakota Bioscience Innovation Grant Program - Yahoo Finance

New gene therapies may soon treat dozens of rare diseases, but million-dollar price tags will put them out of reach for many – The Conversation US

Zolgensma which treats spinal muscular atrophy, a rare genetic disease that damages nerve cells, leading to muscle decay is currently the most expensive drug in the world. A one-time treatment of the life-saving drug for a young child costs US$2.1 million.

While Zolgensmas exorbitant price is an outlier today, by the end of the decade therell be dozens of cell and gene therapies, costing hundreds of thousands to millions of dollars for a single dose. The Food and Drug Administration predicts that by 2025 it will be approving 10 to 20 cell and gene therapies every year.

Im a biotechnology and policy expert focused on improving access to cell and gene therapies. While these forthcoming treatments have the potential to save many lives and ease much suffering, health care systems around the world arent equipped to handle them. Creative new payment systems will be necessary to ensure everyone has equal access to these therapies.

Currently, only 5% of the roughly 7,000 rare diseases have an FDA-approved drug, leaving thousands of conditions without a cure.

But over the past few years, genetic engineering technology has made impressive strides toward the ultimate goal of curing disease by changing a cells genetic instructions.

The resulting gene therapies will be able to treat many diseases at the DNA level in a single dose.

Thousands of diseases are the result of DNA errors, which prevent cells from functioning normally. By directly correcting disease-causing mutations or altering a cells DNA to give the cell new tools to fight disease, gene therapy offers a powerful new approach to medicine.

There are 1,745 gene therapies in development around the world. A large fraction of this research focuses on rare genetic diseases, which affect 400 million people worldwide.

We may soon see cures for rare diseases like sickle cell disease, muscular dystrophy and progeria, a rare and progressive genetic disorder that causes children to age rapidly.

Further into the future, gene therapies may help treat more common conditions, like heart disease and chronic pain.

The problem is these therapies will carry enormous price tags.

Gene therapies are the result of years of research and development totaling hundreds of millions to billions of dollars. Sophisticated manufacturing facilities, highly trained personnel and complex biological materials set gene therapies apart from other drugs.

Pharmaceutical companies say recouping costs, especially for drugs with small numbers of potential patients, means higher prices.

The toll of high prices on health care systems will not be trivial. Consider a gene therapy cure for sickle cell disease, which is expected to be available in the next few years. The estimated price of this treatment is $1.85 million per patient. As a result, economists predict that it could cost a single state Medicare program almost $30 million per year, even assuming only 7% of the eligible population received the treatment.

And thats just one drug. Introducing dozens of similar therapies into the market would strain health care systems and create difficult financial decisions for private insurers.

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One solution for improving patient access to gene therapies would be to simply demand drugmakers charge less money, a tactic recently taken in Germany.

But this comes with a lot of challenges and may mean that companies simply refuse to offer the treatment in certain places.

I think a more balanced and sustainable approach is two-fold. In the short term, itll be important to develop new payment methods that entice insurance companies to cover high-cost therapies and distribute risks across patients, insurance companies and drugmakers. In the long run, improved gene therapy technology will inevitably help lower costs.

For innovative payment models, one tested approach is tying coverage to patient health outcomes. Since these therapies are still experimental and relatively new, there isnt much data to help insurers make the risky decision of whether to cover them. If an insurance company is paying $1 million for a therapy, it had better work.

In outcomes-based models, insurers will either pay for some of the therapy upfront and the rest only if the patient improves, or cover the entire cost upfront and receive a reimbursement if the patient doesnt get better. These models help insurers share financial risk with the drug developers.

Another model is known as the Netflix model and would act as a subscription-based service. Under this model, a state Medicaid program would pay a pharmaceutical company a flat fee for access to unlimited treatments. This would allow a state to provide the treatment to residents who qualify, helping governments balance their budget books while giving drugmakers money upfront.

This model has worked well for improving access to hepatitis C drugs in Louisiana.

On the cost front, the key to improving access will be investing in new technologies that simplify medical procedures. For example, the costly sickle cell gene therapies currently in clinical trials require a series of expensive steps, including a stem cell transplant.

The Bill & Melinda Gates Foundation, the National Institute of Health and Novartis are partnering to develop an alternative approach that would involve a simple injection of gene therapy molecules. The goal of their collaboration is to help bring an affordable sickle cell treatment to patients in Africa and other low-resource settings.

Improving access to gene therapies requires collaboration and compromise across governments, nonprofits, pharmaceutical companies and insurers. Taking proactive steps now to develop innovative payment models and invest in new technologies will help ensure that health care systems are ready to deliver on the promise of gene therapies.

The Bill & Melinda Gates Foundation has provided funding for The Conversation US and provides funding for The Conversation internationally.

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New gene therapies may soon treat dozens of rare diseases, but million-dollar price tags will put them out of reach for many - The Conversation US

An ethical analysis of divergent clinical approaches to the application of genetic testing for autism and s… – Physician’s Weekly

Genetic testing to identify genetic syndromes and copy number variants (CNVs) via whole genome platforms such as chromosome microarray (CMA) or exome sequencing (ES) is routinely performed clinically, and is considered by a variety of organizations and societies to be a first-tier test for individuals with developmental delay (DD), intellectual disability (ID), or autism spectrum disorder (ASD). However, in the context of schizophrenia, though CNVs can have a large effect on risk, genetic testing is not typically a part of routine clinical care, and no clinical practice guidelines recommend testing. This raises the question of whether CNV testing should be similarly performed for individuals with schizophrenia. Here we consider this proposition in light of the history of genetic testing for ID/DD and ASD, and through the application of an ethical analysis designed to enable robust, accountable and justifiable decision-making. Using a systematic framework and application of relevant bioethical principles (beneficence, non-maleficence, autonomy, and justice), our examination highlights that while CNV testing for the indication of ID has considerable benefits, there is currently insufficient evidence to suggest that overall, the potential harms are outweighed by the potential benefits of CNV testing for the sole indications of schizophrenia or ASD. However, although the application of CNV tests for children with ASD or schizophrenia without ID/DD is, strictly speaking, off-label use, there may be clinical utility and benefits substantive enough to outweigh the harms. Research is needed to clarify the harms and benefits of testing in pediatric and adult contexts. Given that genetic counseling has demonstrated benefits for schizophrenia, and has the potential to mitigate many of the potential harms from genetic testing, any decisions to implement genetic testing for schizophrenia should involve high-quality evidence-based genetic counseling. 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

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An ethical analysis of divergent clinical approaches to the application of genetic testing for autism and s... - Physician's Weekly

Opinion: Gene editing can be leveraged for the greater good with appropriate regulations – Varsity

With CRISPR gene editing technology continuing to evolve, many ethical arguments have arisen about its use in humans due to its potential for serious misuse. However, some have argued that it is also unethical not to harness the power of this technology given the enormous potential benefit it poses to humankind. Considering the range of applications of CRISPR and the ease with which it can be applied, it is critical for us to put appropriate regulatory processes and policies in place to mitigate the associated risks.

CRISPR/Cas9 or, as its commonly known, CRISPR is a gene editing technology developed in 2011 that allows researchers to edit plant, animal, and human genes with ease and efficiency. Research leveraging CRISPR has led to new, important findings, such as potential new ways of treating diseases like Alzheimers one of many discoveries made by the research group led by Gerold Schmitt-Ulms, a professor at U of Ts Department of Laboratory Medicine & Pathobiology and a researcher at the Tanz Centre for Research in Neurodegenerative Diseases.

Using CRISPR as a tool to understand and treat diseases

Schmitt-Ulms research group is using CRISPR to generate cell models in order to better understand the pathology of phenomena like Alzheimers disease. In an email to The Varsity, Schmitt-Ulms wrote that his group used CRISPR to introduce mutations into human cells that are known to cause inherited versions of the neurodegenerative diseases [they] study.

Studies in cell and animal models represent critical steps toward gaining the insights necessary to transform these tools into medicines, he added.

The hope among many researchers is that CRISPR could lead to large-scale applications for human health, agriculture, and the conservation of endangered species. Given its ability to easily edit any gene, CRISPR could be used to treat things such as HIV, hemophilia, cancer, cystic fibrosis, and infertility, just to name a few. It could even allow humans to receive organs from other species in life-saving organ transplants.

CRISPR has been described as having the potential to revolutionize disease treatment. In addition to treating diseases in humans, it has the potential to eradicate diseases such as malaria by the genetic modification of the species that are carriers of these diseases. It could also be used to protect endangered species or to fortify crops to improve their nutritional content. However, there are concerns that widespread use of the technology could lead to unpredictable consequences, including the creation of designer babies and irreversible disruption to ecosystems.

Ethical concerns of using the technology

One controversial application of CRISPR is its use in human embryos. Presently, if someone edits the human genome in any way that can be inherited, even in a lab setting, its punishable by up to 10 years in prison in Canada one of the most restrictive gene editing laws in the world. The law does not prevent gene editing on all human cells, but only on so-called germ line cells such as embryonic cells that could be passed on through reproduction. Some researchers have been calling for the Canadian government to modify this law to allow research on human reproduction and embryo development with more ease and efficiency.

While Schmitt-Ulms agrees that CRISPR has made it easier to study just about any disease, he emphasized that we are not ready to bring the technology to humans just yet. The main hurdle to human applications are the challenges associated with delivering this technology safely and ethically, he wrote.

Many of the ethical concerns surrounding the use of germ line cells for research have existed before CRISPR, since they are primarily related to controversy regarding the status of a human embryo. Another unknown factor is whether modifications made to germ lines will persist in future generations, which raises major ethical concerns. Even though we are not at the point where CRISPR can be applied to humans, technological advancements like this can evolve quickly gene editing is already part of our society.

The combination of in vitro sterilization and selection of embryos can already today prevent a subset of severe genetic diseases, including inherited forms of prion diseases that my group studies, Schmitt-Ulms wrote.

Humans have been dramatically altering the genetic realities on this planet ever since they started selecting species for farming, and gene-modified foods were introduced decades ago.

However, due to the scale and speed at which gene editing can be done using CRISPR, he recognizes that unethical applications of the technology [pose] indeed considerable risks.

For example, there could be unintended effects of gene editing in humans because scientists dont yet know the function of every gene in the human genome. Additionally, there are concerns surrounding the development of designer babies with specific physical or psychological features or qualities which could drastically exacerbate societal inequities. Even more insidiously, gene editing could be used for eugenics, which involves encouraging gene selection for certain superior traits in human populations.

Another potential concern is the unpredictable consequences on ecosystems and the environment that could arise from using CRISPR to modify other species and crops. The application of CRISPR for crop modification could be extremely useful for addressing famine in certain countries, but if measures arent taken to ensure equitable access, it could similarly exacerbate inequities around the globe.

CRISPR needs responsible regulation

In some communities, researchers are already conducting gene editing experiments on species that are carriers of diseases transmissible to humans. They are mitigating the risks associated with this type of research by developing safety features to control or reverse genetic modifications among a species in case unintended consequences arise.

The ways CRISPR could be misused and abused are serious and need to be addressed. However, the enormous potential benefits of this technology cannot be ignored. As CRISPR continues to evolve, governmental policies will also have to evolve, and governments should consider the social, environmental, and health risks associated with each application of the technology.

As with any risk management, the strictness of regulations need to scale with the risk an activity poses. Not all CRISPR applications are equally dangerous, Schmitt-Ulms emphasized.

There is also a risk associated with failing to leverage this technology in the future for example, there are a lot of diseases that could be treated with the help of CRISPR.

Researchers are continuing to study and improve CRISPR at a fast pace with the hope of eventually bringing its advancements to humans. Schmitt-Ulms advocates for devoting additional time and resources to developing regulatory frameworks for the safe use of this technology. Many researchers have expressed support for the establishment of an international organization that would provide guidance about the ethical use of gene editing.

As with any new technology, a risk-benefit analysis needs to be done for each new potential use of CRISPR. We as a society need to decide what we are and are not willing to accept.

As Schmitt-Ulms pointed out, humanity has developed powerful technologies that can be directed toward nefarious purposes before. These types of scientific advances need to be paralleled by broad public debate on the safe and ethical use of novel technologies.

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Opinion: Gene editing can be leveraged for the greater good with appropriate regulations - Varsity

Intense exercise could trigger ALS in those with genetic risk – Livescience.com

Exercise may trigger the onset of the deadly nerve disease amyotrophic lateral sclerosis (ALS), a new study finds.

The research showed that people who exercised vigorously, and who also carried genes tied to ALS, developed the disease at younger ages than those who were sedentary. The findings suggest that exercise could exacerbate a genetic predisposition to the devastating disease.

"We are used to thinking of exercise being good. In this unusual case, intense exercise is bad for you," said study co-author Michael Snyder, chair of the Department of Genetics at Stanford University.

ALS is a progressive and fatal neurodegenerative disease that results from the death of motor neurons, or nerve cells. No one knows exactly why this happens. It is also known as Lou Gehrig's disease after the legendary baseball player who was diagnosed on his 36th birthday, after setting the record for playing the most consecutive professional baseball games. (Famous physicist Stephen Hawking was struck by the disease in his early 20s.)

Related: How did Stephen Hawking live so long with ALS?

The role of exercise in the development of ALS was controversial. The disease affects anaerobic fast-twitch muscle fibers, but systematic reviews of past research failed to show a connection between exercise and ALS. Because the disease typically presents later in life, it is often referred to as a "two-hit" disease, meaning that a person may have the genes for the disease (the first hit), but a second switch must be flipped for that person to get sick. The new study suggests that for ALS, frequent and prolonged exercise may be a "second hit" that turns such genes on or off, thereby leading to neuronal death.

For the new study, researchers relied on data from the U.K. Biobank, a biomedical database containing in-depth genetic and health information for half a million people. The researchers first identified individuals who exercised at least two to three days per week. They then used a statistical technique to analyze the relationship between exercise and ALS and found that the risk of ALS was directly proportional to the dose of frequent strenuous, and likely anaerobic, exercise.

In the second part of their study, the researchers asked 36 healthy people to do aerobic exercise, then drew blood to see how that exercise changed the expression of genes known to be associated with ALS, including the most common ALS risk gene: C9orf72. This gene codes for a protein of the same name, which is found in brain cells and other nerve cells, including those that direct movement, according to MedlinePlus, a service of the National Library of Medicine. A mutation in the gene for this protein is found in up to 40% of people with familial ALS, according to the ALS association.

Exercise reduced the expression of C9orf72, which mirrors the decreased expression found in ALS patients with a mutation in this gene.

Overall, of 43 known ALS-related genes, 52% were turned on or off following acute exercise. In the final part of the study, the researchers compared exercise history in ALS patients with a C9orf72 mutation to both ALS patients without a C9orf72 mutation and people without ALS. In ALS patients with the C9orf72 mutation, the more people exercised, the younger they tended to be at diagnosis. For those without the mutation, exercise showed a trend towards increasing likelihood of developing ALS, but that result was not statistically significant..

While strenuous exercise increased the risk of ALS, being sedentary did not decrease the risk of developing ALS, nor did having more body fat.

Snyder was surprised by the results. "I find this whole thing quite remarkable," Snyder told Live Science, "that exercise exacerbates a genetic condition for a disease."

For study co-author Johnathan Cooper-Knock, a researcher and lecturer on genetic neuromuscular diseases at the University of Sheffield in the U.K., the most surprising aspect was the significant number of known ALS risk genes that were affected by acute exercise. "This suggests that exercise could play a role in all forms of ALS, including ALS that we may have previously supposed was purely genetic," he told Live Science.

In Cooper-Knock's view, his research group has likely ended the controversy of exercises role in ALS and showed that physical exercise is a risk factor for the disease. "Our hope is that the community will build on this and take it to the next step, which is to quantify the risk of exercise-induced ALS for individuals based on their personal genetics and environment," he said.

He hopes this will lead to potential prevention measures or at least appropriate counseling. "This will allow us to identify at-risk individuals and offer individualized counseling to allow them to make informed decisions regarding their exercise habits," Cooper-Knock said.

At the moment, the researchers are not recommending that any ALS patient or family members, including individuals with C9orf72 mutations, change their exercise habits. More work needs to be done in a larger cohort, because the way the gene is expressed could vary a lot, the researchers said.

They are, however, advocating for genetic screening of ALS patients to deepen understanding of the roles genetics and environment play in the disease.

As to whether Lou Gehrig's iron streak may have led to his development of ALS, Snyder commented, "It seems very likely."

The findings were published May 26 in the journal The Lancet.

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Intense exercise could trigger ALS in those with genetic risk - Livescience.com

UT Southwestern selected top health care employer in Texas by Forbes – UT Southwestern

UTSouthwestern is committed to offering opportunity as well as innovative support that allows employees across our enterprise to perform at their best and grow their careers. Photo taken pre-pandemic

DALLAS Sept. 3, 2021 UTSouthwestern Medical Center was recognized as the top health care employer in Texas, one of the top 10 employers across all industries in the state, and among the nations Best-in-State employers nationally by Forbes/Statista.

Recommendations from employees as well as indirect recommendations from other workers within the same industries are considered along with survey results that consider work conditions, salary, potential for growth, and diversity among selection factors. The Best-In-State Employers 2021 is created through a survey of 80,000 U.S. employees across 25 industry sectors that take into account employment opportunities at the local and national level. This is the second year UTSouthwestern has been recognized.

UTSouthwesterns William P. Clements Jr. University Hospital is nationally ranked among the top 25 hospitals in eight specialties by U.S. News & World Report and ranked the No. 1 Best Hospital in the Dallas-Fort Worth/North Texas region. The region is the fourth-largest metro area in the U.S. behind New York, Los Angeles and Chicago, the most populous metro area in both Texas and the Southern United States, and the 10th-largest in the Americas.

Technical skills training to adapt and master new software and technologies are part of employment opportunities at UTSouthwestern. Photo taken pre-pandemic

Earlier this year, UTSouthwestern placed among the top 40 institutions Forbes honored asBest Employers for Women 2021 and was ranked No. 3 in the nation onForbes list of Americas Best Employers For New Graduates, placing it in the top 1 percent and highest among academic medical centers. UTSouthwestern.

Other recent workplace honors for UTSouthwestern include:

Career Opportunities

Search for UTSW jobs here.

Among its employment highlights, UTSouthwestern has established online and in-person training and mentoring programs for future management and leadership roles. Photo taken pre-pandemic

UTSouthwestern is committed to offering opportunity as well as innovative support that allows employees across our enterprise to perform at their best and grow their careers. Among its employment highlights, UTSouthwestern has established online and in-person training and mentoring programs for future management and leadership roles; technical skills training to adapt and master new software and technologies; and resources for employee wellness, managing stress and finances, and sharing common interests.

UTSouthwestern partners with diverse professional organizations within the community, including the National Association of Black Accountants, National Black MBA Association Inc., National Society of Hispanic MBAs, and the Association of Latino Professionals in Finance and Accounting (ALPFA), to assure that members are aware of the numerous employment opportunities that exist here. Career development is supported by initiatives such as the Presidents Council on Diversity and Inclusion, Business Resource Groups, the Women in Science and Medicine Advisory Committee; the Committee on the Advancement of Women; the Office of Faculty Diversity and Development; and the Office of Womens Careers.

Resources for employee wellness, managing stress and finances, and sharing common interests are among wellness offerings for UTSouthwestern. Photo taken pre-pandemic

UTSouthwestern is committed to an educational and working environment that provides equal opportunity to all members of the University community. In accordance with federal and state law, the University prohibits unlawful discrimination, including harassment, on the basis of: race; color; religion; national origin; sex, including sexual harassment; age; disability; genetic information; citizenship status; and protected veteran status.

About UTSouthwestern Medical Center

UTSouthwestern, one of the nations premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty has received six Nobel Prizes, and includes 25 members of the National Academy of Sciences, 16 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UTSouthwestern physicians provide care in about 80 specialties to more than 117,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 3 million outpatient visits a year.

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UT Southwestern selected top health care employer in Texas by Forbes - UT Southwestern

Beefing up livestock disaster assistance | Farm & Ranch | willistonherald.com – Williston Daily Herald

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