Scientists at the University of WisconsinMadison have published a proof-of-concept method to correct an inherited form of macular degeneration that causes blindness, and that is currently untreatable.
Andrew Hellpap608-225-5024ahellpap@uwhealth.org
The researchers were able to correct the disease in stem cells from patients with BEST1 mutations by overwhelming broken copies of the gene with many functional copies of BEST1. This approach worked for most, but not all, of the BEST1 mutations that they tested. As an alternative approach for mutations that did not respond to this gene augmentation method, the team used CRISPR-Cas9 gene editing to target and correct the mutations.
A paper chronicling the research, co-led by David Gamm, MD, PhD, professor of ophthalmology and visual sciences in the School of Medicine and Public Health, was published online July 23 in the American Journal of Human Genetics. The study was also led by Kris Saha, PhD, associate professor of biomedical engineering and Wisconsin Institute for Discovery, and Bikash Pattnaik, PhD, assistant professor of pediatrics.
This BEST1 gene encodes a protein that regulates the movement of chloride across a layer of the retina called the retinal pigment epithelium (RPE). Best disease is dominant, meaning that people who inherit only one faulty copy of the BEST1 gene from either their mother or their father will develop the disorder. Mutations in BEST1 cause the retinal layer to break down, resulting in blurred central vision that progresses to irreversible vision loss.
People with Best disease have a wide range of mutations that can affect different parts of the protein, all of which were thought to require complex, individualized gene therapies to fix them, Gamm said. We found that many of these mutations were actually very sensitive to a broader gene therapy method that is already established for other retinal diseases.
Fixing a dominant genetic disease via gene therapy typically requires precise removal or repair of the nonfunctional gene without causing harm to the functional gene a difficult task that is frequently unsuccessful. In contrast, recessive genetic diseases that arise when a person inherits two nonfunctional genes one from each parent can be corrected by a technique called gene augmentation. This well-established process introduces a functional copy of the gene to fill the void.
To use another analogy, dominant mutations produce workers that actively look to sabotage the efforts of their capable coworkers, whereas recessive mutations produce proteins that never show up for work at all, Gamm said. As it turns out, the latter situation is usually simpler to treat than the former.
A team of researchers at the McPherson Eye Research Institute, which Gamm directs, hypothesized that it may be possible to adequately dilute the influence of the nonfunctional BEST1 protein by counter-balancing it with many functional copies of BEST1 protein through gene augmentation.
In the lab, the approach worked in RPE cells derived from induced pluripotent stem cells of patients with most, but not all, of the BEST1 gene mutations they tested. Where gene augmentation did not succeed, the team was able to correct the dysfunction using CRISPR-Cas9 gene editing.
The research was carried out in large part by Divya Sinha, PhD, an assistant scientist in Gamms lab, Ben Steyer, a former MD-PhD student in Sahas lab, and Pawan Shahi, PhD, postdoctoral research associate in Pattnaiks lab. The research team also included Sushmita Roy, PhD, associate professor of biostatics and medical informatics at the UW School of Medicine and Public Health and Wisconsin Institute for Discovery.
The scientists demonstrated that their two-pronged gene therapy strategy may hold potential to treat all Best disease mutations in a highly effective manner.
We were able to reverse the disease in all the cell lines using one method or the other, Gamm said. We were also able to determine which mutations were likely to respond to the first-line gene augmentation strategy, and which would be better served with the second-line gene editing approach.
An additional benefit came into focus as this research progressed, according to Gamm.
Our findings also could be applicable to some dominant genetic mutations that affect tissues elsewhere in the body, he said. Its very exciting.
This work was supported by the National Eye Institute, Foundation Fighting Blindness, McPherson Eye Research Institute Sandra Lemke Trout Chair in Eye Research, Retina Research Foundation Emmett Humble Chair, Sarah E. Slack Prevention of Blindness Fund (a component Fund of the Muskingum County Community Foundation),Research to Prevent Blindness, National Science Foundation, Burroughs Wellcome Fund, Retina Research Foundation Kathryn and Latimer Murfee Chair and Retina Research Foundation M.D. Mathews Professorship, and VitreoRetinal Surgery Foundation. This study was supported in part by a UW Data Science Initiative grant and the UW2020 Initiative.
Read the rest here:
- Study Identifies Breast Cancer Risk and Disease-Causing Mutations in Women Over 65 - Cancer Network - November 28th, 2020
- Scientists say West Africans originally migrated to East Africa - Quartz Africa - November 28th, 2020
- Major new study unveils complexity and vast diversity of Africa's genetic variation - The Conversation CA - November 28th, 2020
- Future Visioning the Role of CRISPR Gene Editing: Navigating Law and Ethics to Regenerate Health and Cure Disease - IPWatchdog.com - November 28th, 2020
- Future Visioning The Role Of CRISPR Gene Editing: Navigating Law And Ethics To Regenerate Health And Cure Disease - Technology - United States -... - November 28th, 2020
- Understanding the immunology of COVID-19 - SelectScience - November 28th, 2020
- Scientists successfully implanted human genes into monkeys to increase their brain mass - Boing Boing - November 28th, 2020
- Thirteen TUM researchers among the most cited worldwide - India Education Diary - November 28th, 2020
- Twist Bioscience Reports Fourth Quarter and Full Year Fiscal 2020 Financial Results - Business Wire - November 28th, 2020
- Spaceflight does some weird things to astronauts bodies - MIT Technology Review - November 28th, 2020
- Amgen To Present At The Evercore ISI Virtual HealthCONx Conference - GuruFocus.com - November 28th, 2020
- How to use precision medicine to personalize COVID-19 treatment according to the patients genes - TheStreet - September 2nd, 2020
- Meiotic chromosome synapsis depends on multivalent SYCE1-SIX6OS1 interactions that are disrupted in cases of human infertility - Science Advances - September 2nd, 2020
- Thought to Be Extinct, New Guinea's Singing Dogs Found Alive in the Wild - Smithsonian Magazine - September 2nd, 2020
- Humans have had mystery DNA for 300,000 yearsand now we might finally know what it is - SYFY WIRE - August 10th, 2020
- The Secret to a Long, Healthy Life Is in the Genes of the Oldest Humans Alive - Singularity Hub - August 10th, 2020
- LogicBio Therapeutics Reports Second Quarter 2020 Financial Results and Provides Business UpdatesFDA Clears IND Application for LB-001 for the... - August 10th, 2020
- Research on Tasmanian devil offers new insights into tackling human cancer - National Science Foundation - August 10th, 2020
- Human Genetics Market 2020 Size by Product Analysis, Application, End-Users, Regional Outlook, Competitive Strategies and Forecast to 2027 - Owned - August 10th, 2020
- University of Texas researchers find mutation that led to 2015-2016 Zika outbreak - Homeland Preparedness News - August 10th, 2020
- Blood lipid levels may be altered in some autistic people - Spectrum - August 10th, 2020
- NIH taps Dr. Lindsey Criswell as director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases - National Institutes of Health - August 10th, 2020
- 'Hyper urban' coyote genomes are growing apart from their city and rural cousins - Massive Science - August 10th, 2020
- Why scientists are worried about a 'Warp Speed' COVID-19 vaccine - New Haven Register - August 10th, 2020
- Gyroscope Announces Appointment of Leaders in Retinal Disease, Gene Therapy and the Complement System to Its Clinical and Scientific Advisory Boards -... - August 10th, 2020
- Noel Rose, Who Demonstrated Autoimmunity Exists, Dies at 92 - The Scientist - August 10th, 2020
- Invasion of the Body Snatchers: Viruses Can Steal Our Genetic Code to Create New Human-Virus Genes - SciTechDaily - August 10th, 2020
- Why Are Only 10% of People Left-Handed? Here's What Scientists Know So Far - ScienceAlert - August 10th, 2020
- Holder pasteurization of donated human milk is effective in inactivating SARS-CoV-2 - CMAJ - August 10th, 2020
- Dinosaur diagnosed with bone cancer that afflicts humans today - CNN - August 10th, 2020
- LogicBio Therapeutics Reports Second Quarter 2020 Financial Results and Provides Business Updates - GlobeNewswire - August 10th, 2020
- The Secret to Healthy Longevity Is in the Genes of the Oldest Humans Alive - Singularity Hub - August 10th, 2020
- BU's COVID-19 Testing Passes Its First Test | BU Today - BU Today - August 10th, 2020
- COVID-19 in Africa: Dampening the storm? - Science - August 10th, 2020
- Pacific Biosciences and Asuragen Collaborate to Develop Assays for Carrier Screening and other Applications Based on SMRT Sequencing Technology and... - August 10th, 2020
- U of T researchers identify molecular switch allowing parasites to survive inside hosts without oxygen - News@UofT - August 9th, 2020
- LUMINEX : MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-Q) - marketscreener.com - August 8th, 2020
- Gaucher Disease Treatment Market Size, Top Companies, Trends, Growth Factors Details by Regions, Types and Applications - Owned - August 8th, 2020
- How studying genetics and lifestyle can shape a healthier MENA region - The European Sting - August 8th, 2020
- Detection of H1 Swine Influenza A Virus Antibodies in Human Serum Samples by Age Group - CDC - August 7th, 2020
- Prevail Therapeutics to Present at 2020 Wedbush PacGrow Healthcare Conference - Stockhouse - August 7th, 2020
- human genetics | Description, Chromosomes, & Inheritance ... - August 6th, 2020
- Human Genetics | Pitt Public Health | University of Pittsburgh - August 6th, 2020
- Triplet Therapeutics To Present at Upcoming Events - Business Wire - August 5th, 2020
- 'Hyper urban' coyote genomes are growing apart their from city and rural cousins - Massive Science - August 5th, 2020
- Baylor genomics teams partner to provide COVID-19 testing for Houston area - Baylor College of Medicine News - August 5th, 2020
- Gaucher Disease Treatment Market (Impact of COVID-19) Top Growing Companies: Acetelion Pharmaceutical (J&J Ltd.), Erad Therapeutic Inc., JCR... - August 5th, 2020
- High-fat Diet and Genetics Lead to Anxiety and Depression in Rats - Newswise - August 5th, 2020
- 'Mono' virus turns on cancer-related genes. Here's how. - Live Science - August 4th, 2020
- Human Challenge Trial Neither Essential Nor Ethically Justified at This Time, Says US Expert Anthony Fauci - Yahoo India News - August 4th, 2020
- ICMR to host global web conference on science, ethics of COVID-19 vaccine starting 4.30 pm today - Firstpost - August 4th, 2020
- Faculty/staff honors: Women in engineering network nod, winning magazine article on geologic hazards and refugees and two national genetics society... - July 31st, 2020
- ENCODE3: Interpreting the human and mouse genomes - Science Codex - July 31st, 2020
- Revealing the intrinsic functioning of human and mouse genomes - Tech Explorist - July 31st, 2020
- Maternal Immune Activation Causes Schizophrenia-like Behaviors in the Offspring through Activation of Immune-Inflammatory, Oxidative and Apoptotic... - July 31st, 2020
- Podcast: The ancient war between genes and disease - Genetic Literacy Project - July 31st, 2020
- Pitt's School of Public Health welcomes students with opera about obstetrician who championed hand-washing - TribLIVE - July 31st, 2020
- BNGO Stock Price: BioNano Genomics Inc. retreats, starts week in the red - FXStreet - July 31st, 2020
- A Genetic Mutation Reveals How the SARS-CoV-2 Virus Strikes - Technology Networks - July 31st, 2020
- 88-Year Old Daniel Smith, Son Of Slave, Tells His Story - Moguldom - July 31st, 2020
- 23andMe Releases Devastating Analysis of Trans-Atlantic Slave Trade - Futurism - July 31st, 2020
- MSU researcher earns grant to study effects of droughts - MSUToday - July 31st, 2020
- Massive Growth in Human Genetics Market Breaking new grounds and touch new level in Upcoming Year by QIAGEN, Agilent Technologies, Thermo Fisher... - July 30th, 2020
- CEO of genome analysis firm: We have the data to prove people will take care of themselves - University of Miami - July 30th, 2020
- Researchers from U of T, Harvard study collective human behaviour amid COVID-19 - News@UofT - July 30th, 2020
- Gene mutations discovered as a trigger for male infertility - BioNews - July 29th, 2020
- Cerevel Therapeutics and Cyclica Announce Research Collaboration to Use Artificial Intelligence to Accelerate Discovery of Novel Medicines in... - July 29th, 2020
- Relatives of coronavirus may have been in bats for decades - Opelika Auburn News - July 29th, 2020
- Link between platelets and Covid-19 virus? - The New Indian Express - July 29th, 2020
- Fortress Biotech Announces Publication of Study on Targeted Next Generation Sequencing for Newborn Screening of Menkes Disease in Molecular Genetics... - July 29th, 2020
- New 23andMe Study Reveals the Genetic Legacy of Slavery in the Americas - Gizmodo - July 29th, 2020
- The Groundbreaking Scientist Who Risked All in Pursuit of His Beliefs - The New York Times - July 29th, 2020
- 23andMe and GSK Head to Clinical Trials With Cancer Drug - MSN Money - July 29th, 2020
- Human Genetics - David Geffen School of Medicine at UCLA - July 29th, 2020
- Discovering how genetic 'dark matter' plays a role in mental illness is just the tip of the iceberg for human health - The Conversation UK - July 29th, 2020
- Prevail Therapeutics Granted Composition of Matter Patent for Experimental Gene Therapy Program PR006 - GlobeNewswire - July 29th, 2020
- The toll of shrinking jaws on human health | Stanford News - Stanford University News - July 28th, 2020
- Global Hereditary Genetic Testing Market (2020 to 2030) - Analysis and Forecast - GlobeNewswire - July 28th, 2020
- Triplet Therapeutics nabs Scholar Rock R&D exec as new CSO - FierceBiotech - July 27th, 2020
- Meet Dr Sarah Gilbert, one of the scientists leading the race to find a coronavirus vaccine - The Indian Express - July 27th, 2020