CRISPR corrects mutation in human embryos

For the first time in the U.S., researchers have used the CRISPR-Cas9 gene-editing system in human embryos to correct a harmful hereditary gene mutation.

Led by Shoukhrat Mitalipov of Oregon Health & Science University, the team injected eggs from healthy donors with sperm from a donor with hypertrophic cardiomyopathy, a common condition characterized by irregular heartbeat and heart failure. People with the disease carry a mutation in one of two copies of their MYBPC3 gene. The researchers simultaneously injected CRISPR-Cas9 components with the sperm to repair the mutation and produce embryos with two healthy copies of the gene.

CRISPR-Cas9 uses guide-RNA molecules to target and cut specific segments of DNA. Natural DNA-repair mechanisms in the cell follow up by filling in the missing pieces.

Mitalipov and colleagues found that in embryos co-injected with sperm and CRISPR components, a highly accurate DNA repair mechanism used the eggs’ healthy copy of the MYBPC3 gene as a template to repair the mutated copy from the sperm (Nature 2017, DOI: 10.1038/nature23305). This improved the proportion of embryos with two healthy copies of MYBPC3 from about 50%, in non-CRISPR-treated embryos, to 70%. In the other 30% of CRISPR-treated embryos, a less-accurate mechanism introduced errors as it repaired the DNA cut.

The researchers found no changes to the embryos’ genome outside the targeted mutation. Previously, off-target edits with CRISPR have made human embryos unviable for clinical use.

“This technology can theoretically be applied to any other heterozygous mutation, such as cystic fibrosis or BRCA,” which is associated with breast and ovarian cancers, said coauthor Paula Amato, also at OHSU, during a press conference this week. “Of course, further research and ethical discussions are necessary before proceeding to clinical trials.”