Hereditary Gene Mutations Can Be Corrected, Reports Landmark Embryo Study, with Implications for MS

For the first time, scientists have shown they can correct gene mutations in human embryos — a breakthrough with implications for multiple sclerosis (MS) and several other diseases.

This landmark study was a collaboration involving scientists at the Salk Institute in La Jolla, California; the Oregon Health & Science University in Portland, and Korea’s Institute for Basic Science. Their study, “Correction of a pathogenic gene mutation in human embryos,” recently appeared in the journal Nature.

More than 10,000 single-gene hereditary disorders can be passed down to future generations, affecting millions of people worldwide. Some are autosomal dominant mutations, meaning that a single copy of a gene from one parent can cause clinical symptoms. Others don’t show symptoms until later in life.

Examples of autosomal dominant mutations include BRCA1 and BRCA2 mutations that increase a woman’s risk of developing breast and ovarian cancer, or the HTT gene responsible for Huntington’s disease.

In the study, researchers focused on a mutation in the MYBPC3 gene that causes hypertrophic cardiomyopathy, a serious and life-threatening heart condition. To correct the mutation, they used a new tool called CRISPR-Cas9. CRISPR functions by finding mutated DNA, snipping out the mutations and replacing them with a correct gene sequence based on matched normal DNA.

After obtaining informed consent, the study generated 75 human embryos from donated eggs and sperm. The sperm donated by the “father” carried a mutation on the MYBPC3 gene. The eggs were normal.

Scientists corrected the gene mutations by injecting sperm into eggs to create normal embryos. CRISPR was used in the sperm; once in contact with normal DNA from the egg, the mutated MYBPC3 sequence was replaced with the normal gene sequence from the mother.

Of the 75 human embryos generated, 72 percent were successfully corrected for the MYBPC3 gene mutation.

The team also showed that this correction could be passed on to future cells, which has been a problem for past researchers.

The study shows it may be possible to correct germline mutations before they are passed on to the offspring. Researchers, however, warn that many studies are still needed to ensure that this approach is safe and effective, and that it has no unintentional side effects.

“Despite remarkable targeting efficiency,” authors concluded, “genome editing approaches must be further optimized before clinical application of germline correction can be considered.”