Researchers at OHSU have devised a method that delivers a 10-fold improvement in the amount of DNA that can be recovered from a single cell to be sequenced and interpreted. The finding, published in the journal Nature Biotechnology, is a big leap forward in the effort to understand cancer development, brain function and immunity. (Getty Images)
Researchers have devised a way to multiply by more than ten-fold the accessible details of gene activity in individual cells. Its a big leap in the effort to understand cancer development, brain function, immunity and other biological processes driven by the complex interactions of multitudes of different cell types.
Organs and tissues are made up of cells that may look the same, but individual cells can actually differ dramatically. Single-cell analysis allows the study of this cell-to-cell variation within an organ, tissue or cancerous tumor. But the research has been hampered by limits on the depth of information that can be gleaned at the single-cell level when working with large numbers of cells.
Andrew Adey, PH.D.
The downside has been the low-quality of single-cell profiles. Our method allows us to get a much more complete profile of any given single cell, said Andrew Adey, Ph.D., senior author of a paper in Nature Biotechnology describing the innovation. Adey is an associate professor of molecular and medical genetics in the OHSU School of Medicine.
He said the new method delivers about a ten-fold improvement in the amount of DNA that can be recovered from a single cell to be sequenced and interpreted. The genetic code is written in DNA in a sequence of units, called bases, that are like letters of an alphabet. Sequencing DNA reveals the order of the bases, and it is the first step to understanding the genetic makeup of a cell and whether particular genes are active or silent.
Single-cell studies are particularly important in understanding cancer. The cells of a tumor can be strikingly diverse. Different cells pick up different DNA mutations as the tumor grows, and some of the mutations and changes in gene activity give rise to sub-populations of tumor cells with new qualities, such as the ability to spread to other body parts or resist anti-cancer drugs.
Adey and colleagues showed that their method can be used to reveal DNA alterations that have emerged in a subset of cells in tumor samples taken from patients with pancreatic cancer. Thats important because it can help researchers understand how populations of tumor cells evolve and become deadly.
For example, you can potentially identify rare cell subtypes within a tumor that are resistant to therapy, Adey said. His team has already begun working with OHSU Knight Cancer Institute researchers testing the single-cell method as a way find out if some of the cells in a patients tumor have evolved resistance to a particular chemo drug or targeted therapy. That knowledge could be used to develop individualized treatment plans for patients.
If you are working with something like a cancer biopsy from a patient, a very small piece of tissue, you really want to make every cell count, you really have to get a lot of info from each single cell, Adey said.
The new method builds on a technique called single-cell combinatorial indexed sequencing, which Adey and colleagues developed earlier. Its a way to generate DNA libraries collections of DNA fragments that can be used to analyze genes and mutations for thousands of single cells at the same time. The process uses an enzymatic reaction to attach primers to the ends of the DNA fragments. They are kind of like handles the sequencer uses to start reading, Adey says.
While the technique greatly increases the number of single cells that can be analyzed in one experiment, it comes with the tradeoff of sparse coverage of readable DNA sequences per cell. To be readable, a primer must be attached at both ends of the DNA fragment, which the reaction accomplishes only half of the time.
The new method results in all library fragments having primers on both ends, while also improving efficiency in other ways. The researchers said the efficiency has the added benefit of reducing sequencing costs by about one third.
The adapters are designed such that standard sequencing recipes can be used instead of the custom workflows and primers that are required for competing methods. That makes the method compatible with many different tests commonly used to explore the state of single cells.
This chemistry can just slot into many other assays, Adey said. People can just start using it.
This research was supported by the National Institutes of Health (grants R01DA047237, R35GM124704, and R01MH113926).
In our interest of ensuring the integrity of our research and as part of our commitment to public transparency, OHSU actively regulates, tracks and manages relationships that our researchers may hold with entities outside of OHSU. In regards to this research, Andrew Adey and OHSU colleague Ryan M. Mulqueen are authors on licensed patents that cover components of the technologies described here. Review details of OHSU's conflict of interest program to find out more about how we manage these business relationships.
- Hunterian Medicine Licenses Inscriptas MAD7 Nuclease to Advance Gene Editing Research and Development - Yahoo Finance - October 17th, 2021
- Precision medicine data dive shows water pill may be viable to test as Alzheimer's treatment - National Institutes of Health - October 17th, 2021
- 4 Biotechs to Watch Amid Rising Prominence of Gene Therapies - Yahoo Finance - October 17th, 2021
- The Zacks Analyst Blog Highlights: CRISPR Therapeutics, Editas Medicine, Sarepta Therapeutics and Beam Therapeutics - Yahoo Finance - October 17th, 2021
- Could an Old Drug Be a New Alzheimers Treatment? - AARP - October 17th, 2021
- 5 Slides: Gene therapy and the promise for rare disease - State of Reform - State of Reform - October 17th, 2021
- Harvard's R&D alliance with Resilience to advance manufacture of complex medicines - Harvard Gazette - October 17th, 2021
- Generation Bio to Present at European Society of Gene and Cell Therapy 2021 Annual Virtual Congress - StreetInsider.com - October 17th, 2021
- Genetic screening test leads to discovery of a family trait - Sanford Health News - October 17th, 2021
- Filling the gaps: connecting genes to diseases through proteins - EurekAlert - October 17th, 2021
- Bone Therapeutics appoints Scientific Advisory Board for iMSC cell and gene therapy platform development - GlobeNewswire - October 17th, 2021
- Polygenic screening of embryos is here, but is it ethical? - The Guardian - October 17th, 2021
- Wolter Earns Young Investigator Award | Newsroom - UNC Health and UNC School of Medicine - October 17th, 2021
- Patient Care on the Precipice of Transformation at Penn Medicine's New Pavilion - pennmedicine.org - October 17th, 2021
- ViaCyte to Present at Alliance for Regenerative Medicine Cell & Gene Meeting on the Mesa - PRNewswire - October 11th, 2021
- CRISPR is revolutionizing medicine its origin story is pretty incredible, too - Freethink - October 11th, 2021
- Longevity Foundation to Fund Geroscience Research with 860M - Labiotech.eu - October 11th, 2021
- Explained | The 2021 Nobel Prize in Physiology or Medicine - The Hindu - October 11th, 2021
- Cancer is a Key Focus in Cell and Gene Therapy Research - PR Web - October 11th, 2021
- Nobel prize in medicine won by US scientists who unlocked the secrets of our sense of touch - Livescience.com - October 11th, 2021
- UK Study Suggests Personalized Medicine May be the Future of Alzheimer's Disease Treatment - UKNow - October 11th, 2021
- Family of black woman hailed as 'mother of modern medicine' to sue company for 'stealing her cells' - The Voice Online - October 11th, 2021
- Most expensive medicine in the world soon to be covered in basic health insurance package - NL Times - October 11th, 2021
- Alzheimer's: The heretical and hopeful role of infection - BBC News - October 11th, 2021
- Follow the Money: CRISPR, Next-Gen Neuroscience, Protein Platforms - Bio-IT World - October 11th, 2021
- Diamyd Medical : The diabetes vaccine Diamyd to be featured in two oral presentations at the International Diabetes Federation Congress -... - October 11th, 2021
- NIH awards UT Southwestern researchers $4.4 million to study the genetic basis of vocal learning - UT Southwestern - October 11th, 2021
- Cancer Profiling Market: Rising cancer cases boost the demand for early diagnosis to drive the market - BioSpace - October 11th, 2021
- State-of-the-art manufacturing facility opens in Scottish capital - Scottish Business News - October 11th, 2021
- New Nobelist David Julius was a standout from the start - University of California - October 11th, 2021
- $14.6 million NIH award will accelerate gene therapy research for rare disorder - Wexner Medical Center - The Ohio State University - October 3rd, 2021
- United States Regenerative Medicine Markets to 2026: Focus on Cell Therapies, Gene Therapies, Progenitor & Stem Cell Therapies, Tissue Engineered... - October 3rd, 2021
- Chardan Analyst: Gene Therapy Stocks Start their Long Ride to the Upside - The Wall Street Transcript - October 3rd, 2021
- UC San Diego Cancer Cell Mapping Research May Improve Chemotherapy - Times of San Diego - October 3rd, 2021
- CATO SMS Appoints Vice President of Regulatory Strategy, Cell and Gene Therapy - PRNewswire - October 3rd, 2021
- How did humans lose their tails? Scientists discover what happened. - Mashable - October 3rd, 2021
- mRNA Could Fight Diseases Such as Alzheimer's and Cancer, With Help of UVA Scientist - University of Virginia - October 3rd, 2021
- Collaboration Aims to Improve GeneType Breast Cancer Test's Utility in African Americans - Clinical OMICs News - October 3rd, 2021
- Grant Awarded to Better Define Gastric Cancer Risks of the Hereditary Diffuse Gastric Cancer Gene CTNNA1 - PRNewswire - October 3rd, 2021
- The Multiple System Atrophy Coalition Announces a Groundbreaking Project to Explore the Genetics of MSA - Johnson City Press (subscription) - October 3rd, 2021
- Protective Biosystems: Parasites to Fight Chemical and Biological Weapons - Global Biodefense - October 3rd, 2021
- Psychiatry on the Brink: Precision Medicine Finally Streamlines Therapeutic Selection - BioSpace - October 3rd, 2021
- DMD Gene Therapy SGT-001 Improves Lung Function in Boys in Trial - Muscular Dystrophy News - October 3rd, 2021
- OncoNano Medicine to Present at The American Association for Cancer Research Virtual Conference on Tumor Immunology and Immunotherapy - Yahoo Finance - October 3rd, 2021
- Scientists discover 14 genes that cause obesity - EurekAlert - October 3rd, 2021
- UNC Awarded $24-million NIH Grant to Improve Genomic, Precision Medicine | Newsroom - UNC Health and UNC School of Medicine - September 24th, 2021
- UNC lands $24M grant to drive more genetic research for precision medicine - WRAL Tech Wire - September 24th, 2021
- The Blueprints of Health - Scientific American - September 24th, 2021
- Rare gene mutations lead to greatly increased risk of fatal chemotherapy toxicity - EurekAlert - September 24th, 2021
- DiNAQOR Appoints Medical Device Leader Mark Dehdashtian to Oversee New U.S.-Based Division, Device Development and Production - Yahoo Finance - September 24th, 2021
- Sio Gene Therapies to Participate in Upcoming Conferences - GlobeNewswire - September 24th, 2021
- Novartis acquires Arctos Medical, expanding optogenetics portfolio to bring gene therapies to patients with severe vision loss | More News | News... - September 24th, 2021
- Backed by Penn Medicine Research, National Task Force Recommends Removing Race from Kidney Function Equation - pennmedicine.org - September 24th, 2021
- Protein Pair Promote Vascularization of Breast and Liver Tumors: Suggest Potential Therapeutic Targets - Genetic Engineering & Biotechnology News - September 24th, 2021
- Novel biomarkers of sepsis occurrence and progression | IJGM - Dove Medical Press - September 24th, 2021
- Michael S. Cartwright, MD, MS Awarded the Jun Kimura Outstanding Educator Award From AANEM - Newswise - September 24th, 2021
- Discovery of Obesity-Causing Genes Could Lead to Drugs to Prevent Weight Gain - University of Virginia - September 24th, 2021
- Vertex's Supplement to a New Drug Submission for KALYDECO (ivacaftor) for Patients with Cystic Fibrosis Between the Ages of 4 Months and 18 Years with... - September 24th, 2021
- STEAMM Rising Initiative announced to better prepare Columbus City students for careers - The Columbus Dispatch - September 24th, 2021
- Abingworth, Gimv and Pfizer back stealthy Swiss startup's $61M round to crack gene therapy delivery - FierceBiotech - September 17th, 2021
- Albert Einstein College of Medicine awarded $5 million for research on intellectual and developmental disabilities - EurekAlert - September 17th, 2021
- ONLINE: When Gene Therapy Meets Reality - Isthmus - September 17th, 2021
- AGC boost pDNA and mRNA capacity with expansion - BioProcess Insider - BioProcess Insider - September 17th, 2021
- Vaccines in your salad? Scientists growing medicine-filled plants to replace injections - Study Finds - September 17th, 2021
- How to beat cancer? Find the genes that help it hide - Scope - September 17th, 2021
- Vertex Announces Letter of Intent With pan-Canadian Pharmaceutical Alliance for Public Reimbursement of CFTR Modulators Extended to Include... - September 17th, 2021
- Baylor College of Medicine Developed a Novel Approach to Select Subjects for Gene Experiments More Convenient and Faster than Fruit Fly Screening... - September 16th, 2021
- 5 Gene Therapy Stocks Back in Focus on AbbVie/Regenxbio Deal - Yahoo Finance - September 16th, 2021
- Albert Einstein College of Medicine Awarded $5 Million for Research on Intellectual and Developmental Disabilities - PRNewswire - September 16th, 2021
- Pioneering Gene Therapy Freed Her of Sickle Cell. Is a Cure at Hand? - The New York Times - September 16th, 2021
- Global Induced Pluripotent Stem Cell (iPSC) Market Report 2021: Focus on Drug Discovery & Toxicity Studies, Academic Research, Cell & Gene... - September 16th, 2021
- Sarepta Therapeutics to Showcase Data from its Gene Therapy - GlobeNewswire - September 16th, 2021
- SNP of the SREK1 gene is associated with COPD in Kashi | COPD - Dove Medical Press - September 16th, 2021
- University of Saskatchewan to Advance Ovarian Cancer Tumor Bank, Genetic Test With Government Grant - Precision Oncology News - September 16th, 2021
- Convergence: Regulatory considerations in advancing gene and cellular therapies - Regulatory Focus - September 16th, 2021
- Cracking the code - The West Australian - September 16th, 2021
- American Gene Technologies Appoints Dr. Robert R. Redfield as Special Advisor to the CEO - PR Web - September 16th, 2021
- Alnylam Submits Marketing Authorization Application to the European Medicines Agency for Investigational Vutrisiran for the Treatment of Hereditary... - September 16th, 2021
- Genetic meds pioneer James Wilson has a new startup, this time in gene editing - MedCity News - September 12th, 2021
- Lung cancer patients in England to receive Amgen drug that targets a gene mutation - Reuters - September 12th, 2021