Scientists have demonstrated an effective way of using a gene-editing tool to correct a disease-causing gene mutation in human embryos and stop it from passing to future generations.
The new technique uses the gene-editing tool CRISPR to target a mutation in nuclear DNA that causes hypertrophic cardiomyopathy, a common genetic heart disease that can cause sudden cardiac death and heart failure. The research, published Aug. 2 in the journal Nature, demonstrates a new method of repairing a disease-causing mutation and preventing it from being inherited by succeeding generations. This is the first time scientists have successfully tested the method on donated clinical-quality human eggs.
“Every generation on would carry this repair because we’ve removed the disease-causing gene variant from that family’s lineage,” said senior author Shoukhrat Mitalipov, Ph.D., who directs the Center for Embryonic Cell and Gene Therapy at OHSU in Portland, Oregon. “By using this technique, it’s possible to reduce the burden of this heritable disease on the family and eventually the human population.”
The study provides new insight into a technique that could apply to thousands of inherited genetic disorders affecting millions of people worldwide. The gene-editing technique described in this study, done in concert with in vitro fertilization, could provide a new avenue for people with known heritable disease-causing genetic mutations to eliminate the risk of passing the disease to their children. It could also increase the success of IVF by increasing the number of healthy embryos.
“If proven safe, this technique could potentially decrease the number of cycles needed for people trying to have children free of genetic disease,” said co-author Paula Amato, M.D., associate professor of obstetrics and gynecology in the OHSU School of Medicine.
The new study focused on the genetic mutation that causes hypertrophic cardiomyopathy. The disease affects an estimated 1 in 500 people and can lead to heart failure and sudden death.
“Although it affects men and women of all ages, it’s a common cause of sudden cardiac arrest in young people, and it could be eliminated in one generation in a particular family,” said co-author Sanjiv Kaul, M.D., a professor of medicine (cardiovascular medicine) in the OHSU School of Medicine and director of the OHSU Knight Cardiovascular Institute.
Researchers worked with healthy donated human oocytes and sperm carrying the genetic mutation that causes cardiomyopathy. Embryos created in this study were used to answer pre-clinical questions about safety and effectiveness. The study noted that “genome editing approaches must be further optimized” before moving to clinical trials.
“This research significantly advances scientific understanding of the procedures that would be necessary to ensure the safety and efficacy of germline gene correction,” said Daniel Dorsa, Ph.D., senior vice president for research at OHSU. “The ethical considerations of moving this technology to clinical trials are complex and deserve significant public engagement before we can answer the broader question of whether it’s in humanity’s interest to alter human genes for future generations.”
Research conducted in this study adhered to guidelines established by OHSU’s Institutional Review Board and additional ad-hoc committees established for scientific and ethical review. Further, the work is consistent with recommendations issued this year by the National Academy of Sciences and the National Academy of Medicine joint panel on human genome editing.
Filed Under: Genomics/Proteomics