DNA-editing method shows promise to treat mouse model of progeria – National Human Genome Research Institute
Posted: January 9, 2021 at 3:06 am
Researchers have successfully used a DNA-editing technique to extend the lifespan of mice with the genetic variation associated with progeria, a rare genetic disease that causes extreme premature aging in children and can significantly shorten their life expectancy. The study was published in the journal Nature, and was a collaboration between the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health; Broad Institute of Harvard and MIT, Boston; and the Vanderbilt University Medical Center, Nashville, Tennessee.
Your browser does not support the video tag.
Base editing for progeria treatmentProgeria is caused by a mutation in the nuclear lamin Agene in which one DNA base C is changed to a T. Researchers used the base editing method, which substitutes a single DNA letter for another without damaging the DNA, to reverse that change. Credit: Ernesto Del Aguila, NHGRI.
DNA is made up of four chemical bases A, C, G and T. Progeria, which is also known as Hutchinson-Gilford progeria syndrome, is caused by a mutation in the nuclear lamin A(LMNA) gene in which one DNA base C is changed to a T. This change increases the production of the toxic protein progerin, which causes the rapid aging process.
Approximately 1 in 4 million children are diagnosed with progeria within the first two years of birth, and virtually all of these children develop health issues in childhood and adolescence that are normally associated with old age, including cardiovascular disease (heart attacks and strokes), hair loss, skeletal problems, subcutaneous fat loss and hardened skin.
For this study, researchers used a breakthrough DNA-editing technique called base editing, which substitutes a single DNA letter for another without damaging the DNA, to study how changing this mutation might affect progeria-like symptoms in mice.
"The toll of this devastating illness on affected children and their families cannot be overstated," said Francis S. Collins, M.D., Ph.D., a senior investigator in NHGRI's Medical Genomics and Metabolic Genetics Branch, NIH director and a corresponding author on the paper. "The fact that a single specific mutation causes the disease in nearly all affected children made us realize that we might have tools to fix the root cause. These tools could only be developed thanks to long-term investments in basic genomics research.
The toll of this devastating illness on affected children and their families cannot be overstated.The fact that a single specific mutation causes the disease in nearly all affected children made us realize that we might have tools to fix the root cause. These tools could only be developed thanks to long-term investments in basic genomics research.
The study follows another recent milestone for progeria research, as the U.S. Food and Drug Administration approved the first treatment for progeria in November 2020, a drug called lonafarnib. The drug therapy provides some life extension, but it is not a cure. The DNA-editing method may provide an additional and even more dramatic treatment option in the future.
David Liu, Ph.D., and his lab at the Broad Institute developed the base-editing method in 2016, funded in part by NHGRI.
"CRISPR editing, while revolutionary, cannot yet make precise DNA changes in many kinds of cells," said Dr. Liu, a senior author on the paper. "The base-editing technique we've developed is like a find-and-replace function in a word processor. It is extremely efficient in converting one base pair to another, which we believed would be powerful in treating a disease like progeria.
To test the effectiveness of their base-editing method, the team initially collaborated with the Progeria Research Foundation to obtain connective tissue cells from progeria patients. The team used the base editor on theLMNAgene within the patients cells in a laboratory setting. The treatment fixed the mutation in 90% of the cells.
The Progeria Research Foundation was thrilled to collaborate on this seminal study with Dr. Collinss group at the NIH and Dr. Lius group at Broad Institute, said Leslie Gordon, M.D., Ph.D., a co-author and medical director of The Progeria Research Foundation, which partially funded the study. These study results present an exciting new pathway for investigation into new treatments and the cure for children with progeria.
Following this success, the researchers tested the gene-editing technique by delivering a single intravenous injection of the DNA-editing mix into nearly a dozen mice with the progeria-causing mutation soon after birth. The gene editor successfully restored the normal DNA sequence of theLMNAgene in a significant percentage of cells in various organs, including the heart and aorta.
Many of the mice cell types still maintained the corrected DNA sequence six months after the treatment. In the aorta, the results were even better than expected, as the edited cells seemed to have replaced those that carried the progeria mutation and dropped out from early deterioration. Most dramatically, the treated mice's lifespan increased from seven months to almost 1.5 years. The average normal lifespan of the mice used in the study is two years.
As a physician-scientist, its incredibly exciting to think that an idea youve been working on in the laboratory might actually have therapeutic benefit, said Jonathan D. Brown, M.D., assistant professor of medicine in the Division of Cardiovascular Medicine at Vanderbilt University Medical Center. Ultimately our goal will be to try to develop this for humans, but there are additional key questions that we need to first address in these model systems.
Funding for the study was supported in part by NHGRI, the NIH Common Fund, the National Institute of Allergy and Infectious Diseases, the National Institute of Biomedical Imaging and Engineering, the National Institute of General Medical Sciences, the National Heart, Lung and Blood Institute and the National Center for Advancing Translational Sciences.
View original post here:
DNA-editing method shows promise to treat mouse model of progeria - National Human Genome Research Institute
- Springfield National Weather Service radar scheduled outage coming, will last about a week - KOLR - OzarksFirst.com - February 25th, 2021
- Global Military Aircraft Modernization and Upgrade and Retrofit Markets to 2024: Incorporation of CNS Systems in aircraft and Emergence of SVAB -... - February 25th, 2021
- Real-Time Communication with Dreaming Person Possible, Says Study | The Weather Channel - Articles from The Weather Channel | weather.com - The... - February 25th, 2021
- Canned Soups Market Forecast to 2027 - COVID-19 Impact and Global Analysis By Type, Category, Processing, and Distribution Channel - GlobeNewswire - February 25th, 2021
- Star Royalties Closes Second US$6 Million Installment of US$18 Million Stream Financing for the Restart of the Copperstone Gold Mine - Junior Mining... - February 25th, 2021
- Norwegian Army Adding 20 CV90s to Its Fleet - Business Wire - February 25th, 2021
- Calico Purring Right Along With Life Extension Research - Nanalyze - February 1st, 2021
- Get healthy in Feb. with AgriLife - Pleasanton Express - February 1st, 2021
- Wellness Supplements Market Statistics 2021- Industry Insights and COVID-19 impact analysis with Future Opportunities 2027 | Life Extension, OPTAVIA,... - February 1st, 2021
- Great Panther Files NI 43-101 Technical Report for the Tucano Gold Mine and Provides Update on Exploration Strategy and Programs for 2021 - PRNewswire - February 1st, 2021
- Sweden Looks to the Past to Prepare for Its Defense Future - Defense & Security Monitor - January 29th, 2021
- Yamana Gold Provides 2021-2023 Guidance and Ten-Year Overview - GlobeNewswire - January 29th, 2021
- Here are the challenges involved in building the future US Navy - DefenseNews.com - January 25th, 2021
- Divine Flavor adopts StePac' modified atmosphere standing pouches for extending produce shelf life in the retail sector - PRNewswire - January 25th, 2021
- miRagen Therapeutics Announces Company Name Change to Viridian Therapeutics and New Executive Appointments, Including Expansion of Leadership Team -... - January 25th, 2021
- Capstone Advances Two Operational Growth Projects to Sustain 200 Mlbs Copper Production Starting in 2022 - Business Wire - January 25th, 2021
- 2 More Drugs Recommended To Treat Covid In UK, But Not In US - Kaiser Health News - January 12th, 2021
- The Venture Bros: 10 Biggest Twists In The Series | CBR - CBR - Comic Book Resources - January 12th, 2021
- Digital twins and design innovation - Engineer Live - January 9th, 2021
- Harpoon Therapeutics : Clin Cancer Res 2021; OnlineFirst version Jan 6, 2021 - Marketscreener.com - January 9th, 2021
- Massive Science Year in Review: 2020 edition - Massive Science - January 9th, 2021
- Panthera began dosing volunteers in AstraZeneca's phase III of its long-acting antibody combination AZD7442 for the prevention of COVID-19 at its... - January 9th, 2021
- National Guard troops to take back seat as Trump addresses supporters rallying to his call to overturn the election - Washington Examiner - January 9th, 2021
- Several AF fighter jets, combat helicopters to be overhauled to boost air power - Daily Mirror - January 9th, 2021
- Looking At Year Seven On This Cancerversary - Curetoday.com - January 5th, 2021
- JPT Mature Fields and Well Revitalization - Journal of Petroleum Technology - January 5th, 2021
- The 6 big military space stories of 2020 - C4ISRNet - January 5th, 2021
- Comprehensive Report on Magnolia Bark Extract Market 2021 | Trends, Growth Demand, Opportunities & Forecast To 2027 - LionLowdown - January 5th, 2021
- Midlife refit of Scripps' Research Vessel Roger Revelle completed - Research vessel (R/V) Roger Revelle is back at work after a midlife refit... - January 5th, 2021
- 2020: A year of challenge and achievement for Indian nuclear sector - The Siasat Daily - January 5th, 2021
- Equinor stakes NOK 3 billion to improve Statfjord Ost oil recovery - WorldOil - December 28th, 2020
- Antibody study aims to protect those exposed to coronavirus from illness - The Jerusalem Post - December 28th, 2020
- Five Persistent Misconceptions About Modernizing The US ICBM Force - Forbes - December 28th, 2020
- Commercial constellations don't live up to the hype: Euroconsult - SatelliteProME.com - December 14th, 2020
- Global Antioxidant Supplement Market Proceeds To Witness Huge Upswing Over Assessment Period by 2025 - The Courier - December 14th, 2020
- The end of coal? Why investors aren't buying the myth of the industry's 'renaissance' - The Guardian - December 14th, 2020
- Fiore Gold Reports Two Year Mine Life Extension at Its Pan Mine, Nevada - Yahoo Finance - December 10th, 2020
- Crescendo Biologics Expands its Ongoing Collaboration with Takeda - Business Wire - December 10th, 2020
- The 10 Best Creatine Supplements in 2020 - Healthline - December 10th, 2020
- EPZ calls for continued nuclear power in the Netherlands - Nuclear Engineering - December 10th, 2020
- The Global Military Aircraft Modernization and Upgrade and Retrofit Market is expected to grow by $ 2.61 bn during 2020-2024 progressing at a CAGR of... - December 10th, 2020
- Controlled Intelligent Packaging, Preservation and Shelf-Life Extension Market to Witness Widespread Expansion During 2020 to 2026 Cargill Inc.... - December 10th, 2020
- Shelf Life Extension Ingredients Market Demand, Growth, Opportunities and Analysis Of Top Key Player Forecast To 2028 - Murphy's Hockey Law - December 10th, 2020
- SABCS: Novartis touts Kisqali's 5-year breast cancer survival, advantage over Pfizer's Ibrance - FiercePharma - December 10th, 2020
- Satellite capacity pricing declines slow, but price pressure expected to increase with new supply entering service in 2023 - Geospatial World - December 6th, 2020
- Team Trump's 2022 budget plan; COVID canks conference; Raytheon, C3.ai team up; and more. - Defense One - December 6th, 2020
- Researchers Think Megastructures Can Help Seed Life Throughout the Galaxy - VICE - December 6th, 2020
- Dehydroepiandrosterone(DHEA) Market 2020-2025 with Growth Factors and Trends with Focusing Key players like BulkSupplements, Natrol, Jarrow Formulas,... - December 6th, 2020
- Shelf Life Extension Ingredients Market Analysis of Key Players, End User, Demand and Consumption By 2028 - The Haitian-Caribbean News Network - December 1st, 2020
- Lubbock weather radar to be down for 2 weeks - Plainview Daily Herald - November 28th, 2020
- Switzerland extends life of CV90s - Jane's - November 28th, 2020
- Impact of COVID-19 on Oral Probiotics Market 2020 Industry Insight, Segment by Key Companies, Countries, Types, Applications and Forecast to 2026 -... - November 28th, 2020
- Incremental Sales to Drive the Cold Plasma Market by 2026 - The Market Feed - November 28th, 2020
- Flight Tests to Show B61-12 Will Work on Air Force's Newest Fighter Jet - I-Connect007 - November 26th, 2020
- An F-35A Dropped An Inert B61-12 Nuclear Bomb During Supersonic Flight For The First Time - The Aviationist - November 26th, 2020
- Flight tests to show B61-12 will work on Air Forces newest fighter jet - Newswise - November 26th, 2020
- Global Bilberry Extract Products Market To Witness Huge Gains Over 2020-2026 - The Courier - November 26th, 2020
- Traditional launch services may not suit the needs of the future Space Force - SpaceNews - November 26th, 2020
- Natural sleeping pills: What are they? - Medical News Today - November 23rd, 2020
- Adagio Therapeutics COVID-19 Antibody Demonstrates Best-in-Class Breadth and Potency Against a Range of Coronaviruses that Pose Human Threat |... - November 23rd, 2020
- Infrastructure and Energy Alternatives, Inc. Extends Service Offering to Wind Customers Through Formation of New Renewable Energy Services Group -... - November 23rd, 2020
- Family fight to make more memories with daughter after pandemic robs them of precious time - North Wales Live - November 23rd, 2020
- NY Power Authority Announces First Milestone of Project to Extend Operating Life of New York's Largest Power Plant - Automation.com - November 18th, 2020
- Cryonics Technology Market Size & Revenue Analysis | Praxair, Cellulis, Cryologics, Cryotherm, KrioRus - The Think Curiouser - November 18th, 2020
- Minot's weather radar will be out of service for approximately one week for scheduled upgrades - Minot Daily News - November 18th, 2020
- Cryonics Technology Market 2020 to Global Forecast 2023 By Key Companies Praxair, Cellulis, Cryologics, Cryotherm, KrioRus, VWR, Thermo Fisher... - November 18th, 2020
- Inside The Navy's Top Aggressor Squadron That Is About To Trade Its Hornets For Super Hornets - The Drive - November 18th, 2020
- Antioxidant Supplement Market Bolstered by Emerging New Advancements, Says QYR | NOW, Vibrant Health, AST R-ALA, GNC - The Think Curiouser - November 18th, 2020
- Why Blade Runner is the best sci-fi movie of all time - Looper - November 18th, 2020
- Column: Just How Old Is 'Old Age' in The Future? - Southern Pines Pilot - November 8th, 2020
- Oral Probiotics Market Outlook, Global Key Players and Covid-19 Impact by 2026 | Oragenics, Life Extension, TheraBreath and Others - TechnoWeekly - November 8th, 2020
- 10 Sci-Fi Movies That Only Make Sense On A Rewatch | ScreenRant - Screen Rant - November 8th, 2020
- Emergent BioSolutions Reports Financial Results for Third Quarter and Nine Months Ended September 30, 2020 and Updates Full Year 2020 Guidance - Yahoo... - November 5th, 2020
- Insights on the In-Space Manufacturing, Servicing, and Transportation Global Market to 2030 - Increasing Developments in On-Orbit Space Capabilities... - November 5th, 2020
- MJR completes work on TSHD Heortnesse - Dredging Today - November 5th, 2020
- Global Glucose Tolerance Test Market 2020 Covid 19 Analysis, Market Size, Market Growth, Competitive Strategies, and Worldwide Demand 2027 - BCFocus - November 5th, 2020
- Lingonberry Extract Market: Qualitative analysis of the leading players and competitive industry scenario | Shanghai Freemen, Natrol, Source Naturals,... - November 5th, 2020
- Cryonics Technology Market 2020 Industry Size, Trends, Global Growth, Insights And Forecast Research Report 2025 - The Think Curiouser - November 5th, 2020
- Antioxidant Supplement Market 2026 Industry Trends, Size, Growth Insight, Share, Emerging Technologies, Share, Competitive, Regional, And Global... - November 5th, 2020
- Impact Of Covid 19 On Bilberry Extract Products Market 2020 Industry Challenges Business Overview And Forecast Research Study 2026 - TechnoWeekly - November 5th, 2020