By Melissa Healy Los Angeles Times (TNS)
Using a powerful gene-editing technique, scientists have rid human embryos of a mutation that causes an inherited form of heart disease often deadly to healthy young athletes and adults in their prime.
The experiment marks the first time that scientists have altered the human genome to ensure a disease-causing mutation would disappear not only from the DNA of the subject on which its performed, but from the genes of his or her progeny as well.
The controversial procedure, known as germ-line editing, was conducted at Oregon Health & Science University using human embryos expressly created for the purpose. It was reported Wednesday in the journal Nature.
The new research comes less than six months after the National Academies of Science, Engineering and Medicine recommended that scientists limit their trials of human germ-line editing to diseases that could not be treated with reasonable alternatives at least for now.
In a bid to make the experiment relevant to real-life dilemmas faced by parents who carry genes for inherited diseases, the researchers focused their editing efforts on a mutation that causes inherited hypertrophic cardiomyopathy.
In this genetic condition, a parent who carries one normal and one faulty copy of a the MYBPC3 gene has a 50-50 chance of passing that mutation on to his or her offspring. If the child inherits the mutation, his or her heart muscle is likely to grow prematurely weak and stiff, causing heart failure and often early death.
In diseases where one parent carries such an autosomal dominant mutation, a couple will often seek the assistance of fertility doctors to minimize the risk of passing such a mutation on to a child. A womans egg production is medically stimulated, and eggs and sperm meet in a lab a process called in vitro fertilization. Then embryologists inspect the resulting embryos, cull the ones that have inherited an unwanted mutation, and transfer only unaffected embryos into a womans uterus to be carried to term.
In the new research, researchers set out to test whether germ-line gene editing could make the process of choosing healthy embryos more effective and efficient by creating more of them.
In the end, their experiment showed it could. The targeted correction of a disease-causing gene carried by a single parent can potentially rescue a substantial portion of mutant human embryos, thus increasing the number of embryos available for transfer, the authors wrote in Nature. Co-author Dr. Paula Amato, an Oregon Health & Science University (OHSU) professor of obstetrics and gynecology, said the technique could potentially decrease the number of cycles needed for people trying to have children free of genetic disease if its found safe for use in fertility clinics.
Along the way, though, many of the researchers findings were scientifically surprising. Long-feared effects of germ-line editing, including collateral damage to off-target genetic sequences, scarcely materialized. And mosaicism, a phenomenon in which edited DNA appears in some but not all cells, was found to be minimal.
The studys lead author, OHSU biologist Shoukhrat Mitalipov, called these exciting and surprising moments. But he cautioned that there is room to improve the techniques demonstrated to produce mutation-free embryos. As for conducting human clinical trials of the germ-line correction, he said those would have to wait until results showed a near-perfect level of efficiency and accuracy, and could be limited by state and federal regulations.
Eventually, Mitalipov said, such germ-line gene editing might also make it easier for parents who carry other gene mutations that follow a similar pattern of inheritance including some that cause breast and ovarian cancers, cystic fibrosis and muscular dystrophy to have healthy children who would not pass those genes to their own offspring.
There is still a long road ahead, predicted Mitalipov, who heads the Center for Embryonic Cell and Gene Therapy at the Portland university.
The research drew a mix of praise and concern from experts in genetic medicine.
Dr. Richard O. Hynes, who co-chaired the National Academies report issued in February, called the new study very good science that advances understanding of genetic repair on many fronts. Hynes, who was not involved with the latest research effort, said he was pleasantly surprised by researchers clever modifications and their outcomes.
Its likely to become feasible, technically not tomorrow, not next year, but in some foreseeable time. Less than a decade, Id say, said Haynes, a biologist and cancer researcher at MIT and the Howard Hughes Medical Institute.
University of California, Berkeley molecular and cell biologist Jennifer Doudna, one of pioneers of the CRISPR-Cas9 gene-editing technique, acknowledged the new research highlights a prospective use of gene editing for one inherited disease and offers some insights into the process.
But Doudna questioned how broadly the experiments promising results would apply to other inherited diseases. She said she does not believe the use of germ-line editing as a means to improve efficiency at infertility clinics meets the criteria laid out by the National Academies of Science, which urged that the techniques only be explored as treatment for diseases with no reasonable alternative.
Already, 50 percent of embryos would be normal, said Doudna. Why not just implant those?
Doudna said she worried that the new findings will encourage people to proceed down this road before the scientific and ethical implications of germ-line editing have been fully considered.
A large group of experts concluded that clinical use should not proceed until and unless theres broad societal consensus, and that just hasnt happened, Doudna said. This study underscores the urgency of having those debates. Because its coming.
What is clear is that the researchers a multinational team of geneticists, cardiologists, fertility experts and embryologists from OHSU and from labs in South Korea and China tried a number of innovations in an effort to improve the safety, efficiency and fidelity of gene editing. And most yielded promising results.
After retrieving eggs from 12 healthy female volunteers, researchers simultaneously performed two steps that had never been combined in a lab: At the same moment that they fertilized the eggs with the sperm of a man who carried a single copy of the mutated gene, they introduced the CRISPR-Cas9 repair machinery.
The resulting embryos took up the genetic-editing program so efficiently and uniformly that, after five days of incubation, 72.4 percent of the embryos (42 of 58) created and tested were free of the MYBPC3 mutation. By comparison, when sperm carrying the single mutation was used to fertilize eggs without any genetic manipulation, just 47.4 percent of embryos were free of the mutation linked to the deadly heart condition.
The researchers believe the timing and the techniques they used prompted the embryos to rely on the healthy maternal copy of the gene as a model for fixing the MYBPC3 mutation, and not a repair template they introduced alongside the editing machinery when the eggs were fertilized. Only one of the 42 embryos used the introduced template for repair. The scientists contrasted this process to the DNA-repair mechanism operating in stem cells, which do use repair templates.
As the embryos cells divided and they matured to the blastocyst stage the point at which they would usually be ready for transfer to a womans uterus they did so normally. After extensive testing, the embryos were used to make embryonic stem-cell lines, which are stored in liquid nitrogen and can be used in future research.
Researchers also noted that genetic mosaicism a concern raised by earlier experimental efforts at gene editing was virtually absent from the 42 embryos that were free of the disease-causing mutation. Only one of the 42 embryos exhibited mosaicism, a condition in which cells did not all carry the same mutation-free genetic code.
MITs Hynes said such findings offer important insights into how human embryos grow, develop and respond to anomalies, and will help families facing infertility and inherited illnesses.
Human embryogenesis is clearly different from that of a mouse, which we know a lot about, said Hynes. That needs to be studied in human embryos, and theres no other way to do it.
The results of the current study are not low enough yet for most applications certainly not for clinical applications, but its a big step forward, he added.
While calling the new research very nice science, Hynes downplayed fears that germ-line editing would soon lead to tinkering with such attributes as looks, personality traits and intelligence in human children. Were not looking at designed babies around the corner not for a long time, he said.
But we need to take advantage of the time and space we now have, he said, to make decisions about which uses of the technique are legitimate and which are not.
- Cancer gene therapy backed by Blackstone gets trial win - BioPharma Dive - December 6th, 2019
- Counterculture 73: Summer Jam, Timothy Leary and the Sexual Revolution - Rolling Stone - December 6th, 2019
- Precision Cancer Therapies Market Size, Status and Forecast 2025 Trends, Size, Drivers, Strategies, Products and - The Market Stats News - December 6th, 2019
- World AIDS Day 2019: 37.9M people worldwide were living with HIV at the end of 2018 - USA TODAY - December 2nd, 2019
- Global Parkinsons Disease Treatment Market 2019 Analysis by Industry Growth, Size, Share, Trends and Forecast by 2025 - Eastlake Times - November 30th, 2019
- Diabetic foot wounds kill millions, but high-tech solutions and teamwork are making a difference - Thehour.com - November 28th, 2019
- Macular Degeneration Treatment Market and its Future Outlook and Trend During the Period of 2019 2026 - The Chicago Sentinel - November 25th, 2019
- Edited Transcript of BLFS earnings conference call or presentation 12-Nov-19 9:30pm GMT - Yahoo Finance - November 20th, 2019
- U.S. stem cell clinic offering unapproved therapies brings direct-to-consumer marketing to Ottawa - Ottawa Citizen - November 18th, 2019
- Hemophilia Treatment Market Dynamics, Pin-Point Analysis, Comprehensive Landscape, Demand Key Factors, Market Segments Regions, Therapy For Hemophilia... - November 18th, 2019
- Global Regenerative Therapies for Osteoarthritis Market Insights 2019 : Acelity, Mesoblast, Nuo Therapeutics, Astellas Pharma - Breakaway Trends - November 18th, 2019
- Abuse in cell banking services a global problem - Bioprocess Insider - BioProcess Insider - November 14th, 2019
- Anti-Aging Products and Therapies Market Outlook: Investors Still Miss the Big Assessment - The Market Journal - November 11th, 2019
- Tip Sheet: A clever way to make an AIDS vaccine; how a common cancer mutation actually drives cancer; and a new process that regulates red blood cell... - November 9th, 2019
- Global Cell Therapy Technologies Market Industry Analysis And Forecast (2018-2026) - The Market Expedition - November 6th, 2019
- Davenport & Company Upped By $3.56 Million Its Sgmo (SGMO) Holding; EMPOWER CLINICS ORDINARY SHARES (EPWCF) Shorts Raised By 2360% - MS Wkly - November 6th, 2019
- Dr Batra's have launched a new genetics-based therapy that predicts future diseases - Gulf Today - October 31st, 2019
- Deepak Chopra Has Never Been Sick - The New Yorker - October 18th, 2019
- The Patient Perspective On Patient Centricity Insights From A Veteran Of 5 Clinical Trials - Clinical Leader - October 12th, 2019
- Parkinsons Disease Treatment Analysis, Trends, Top Manufacturers, Share, Growth, Statistics, Opportunities & Forecast to 2025 - The Ukiah Post - October 11th, 2019
- Transfusion-dependent Anemia Treatment Market Gain Impetus due to the Growing Demand over 2019 2029 - Herald Space - October 1st, 2019
- Non-viral Gene Therapy will now accelerate cancer study - Industry Reporter - September 28th, 2019
- Social Impact Heroes: How Lynn OConnor Vos and the Muscular Dystrophy Association are helping to raise billions of dollars to fund research to... - September 28th, 2019
- Pollard and Norris in the race for Pos. 2 of the Public Hospital District 4 - Snoqualmie Valley Record - September 28th, 2019
- Nearly Half of Poland's SMA Patients on Track to Get Spinraza, Experts Say - SMA News Today - September 28th, 2019
- Prospective Study Characterizes PCa Risk Linked to BRCA1, BRCA2 Mutations - Renal and Urology News - September 28th, 2019
- Precision Cancer Therapies Market Forecast Research Reports Offers Key Insights 2017 2025 - Space Market Research - September 28th, 2019
- Google bans ads for 'bad actors' selling 'deceptive treatments' - BioEdge - September 22nd, 2019
- Texas State To Expand Round Rock Campus Programs, Services - Round Rock, TX Patch - September 22nd, 2019
- Transfusion-dependent Anemia Treatment Market Size, Status and Growth Opportunities by 2025 - The Market Plan - September 22nd, 2019
- Chemotherapy Drugs Market Strategies, Major Industry Participants, Marketing Channels and Forecast To2018 2028 - Commerce Gazette - September 22nd, 2019
- Targeted Cancer Therapies Market Regional Landscape, Production, Sales & Consumption Status and Prospects 2025 - Commerce Gazette - September 22nd, 2019
- Precision Cancer Therapies Market to Witness Comprehensive Growth by 2017 2025 - Technology Trend - September 22nd, 2019
- Biological Product Manufacturing Market Analysis, Size, Regional Outlook, Share, Trend, Growth, Analysis and Forecast - Rapid News Network - September 22nd, 2019
- Google Bans Advertising on Unproven Medical Treatments (like Stem Cells) - Bedford Bulletin - September 22nd, 2019
- 4 Barriers To Cell And Gene Therapy Development For Rare ... - May 18th, 2019
- Gene Therapy: The New Frontier for Inherited Retinal Disease - April 16th, 2019
- Nutrition : The Addiction Recovery Guide - March 25th, 2019
- F.D.A. Speeds Review of Gene Therapies, Vowing to Target ... - February 17th, 2019
- Cell and Gene Therapy Center - IQVIA - December 24th, 2018
- resurrection-clinics.eu - August 24th, 2018
- Hacking Your Genes Has Never Been Easier - Outside Magazine - September 8th, 2017
- FDA approves first cell-based gene therapy for use in the United States - Gears Of Biz - September 8th, 2017
- Quick Hits: Withdrawn Leukemia Drug Returning, Drugmaker in $58M Settlement Over Sales Reps, and More - MedShadow (registration) (blog) - September 8th, 2017
- FDA Approves New Cancer Treatment - Alive For Football - September 5th, 2017
- Global Cancer Biological Therapy Analysis & Forecast 2016 to 2023 - Digital Journal - September 5th, 2017
- How one California county is fighting high-priced surgeries - Los Angeles Times - September 2nd, 2017
- New 'hit-and-run' gene editing tool temporarily rewrites genetics to treat cancer and HIV - GeekWire - September 2nd, 2017
- Australian Market Declines - Markets Insider - August 29th, 2017
- New Stanford drug saves child with deadly genetic disease - The Mercury News - August 25th, 2017
- Orphan Diseases Market Key Players analysis ... - Digital Journal - Digital Journal - August 25th, 2017
- Gene Editing in Human Embryos Leaps ForwardHere's the Science - Singularity Hub - August 22nd, 2017
- Global Cancer Biological Therapy Market 2017 Size, Development Status, Type and Application, Segmentation ... - Digital Journal - August 22nd, 2017
- Traditional Therapy Clinics Ltd (TTC.AX) Money Flow Index Levels in Focus - Stock Daily Review - August 22nd, 2017
- Sodium Iodide Symporter for Nuclear Molecular Imaging and ... - August 13th, 2017
- Biological bypass shows promise in coronary artery disease - Medical Xpress - August 12th, 2017
- Cardiovascular disease cure? One session of THIS could help treat condition - Express.co.uk - August 9th, 2017
- Understanding the muscle behind global duchenne muscular dystrophy market - WhaTech - August 9th, 2017
- Proton Therapy: How It Could Change The Outcome of Paediatric Cancer - HuffPost - August 5th, 2017
- Wilson's Disease Market: Unmet Needs of Patient Population to Inspire Players for Improved Treatment Options - Edition Truth - August 5th, 2017
- Head and Neck Cancer Therapeutics Market is Expected to Generate Huge Profits by 2024 - MilTech - July 12th, 2017
- Cancer Biological Therapy market is rising with potential rate at CAGR of 4.7 % till 2023 - MENAFN.COM - July 11th, 2017
- Stem cell therapies breaking barriers - Guardian (blog) - July 9th, 2017
- Alternative Cancer Clinics - Immunotherapy for Cancer - July 8th, 2017
- Advanced Gene-Targeted Therapies - Alternative Cancer Clinics - July 8th, 2017
- Cure for ageing could lie in gene therapy | WIRED UK - July 1st, 2017
- Digital Journal: A Global Digital Media Network - Digital Journal (press release) - July 1st, 2017
- Gene Therapy Market - Size, Share, industry, Forecast ... - November 30th, 2016
- Medi-Cal: Medi-Cal Update - Clinics and Hospitals | May ... - November 23rd, 2016
- Gene Therapy: Chinese Researching Gene Replacement - September 25th, 2015
- Home Page of the Human Gene and Cell Therapy Center - August 29th, 2015