The team used CRISPR to successfully correct a mutation causing the often-fatal heart condition, hypertrophic cardiomyopathy (HCM), with significantly improved efficiency and accuracy than previous efforts.
'Every generation on would carry this repair because we've removed the disease-causing gene variant from that family's lineage,' said senior author Professor Shoukhrat Mitalipov of the Oregon Health and Science University, Portland. 'By using this technique, it's possible to reduce the burden of this heritable disease on the family and eventually the human population.'
The scientists used sperm donated by a man carrying a mutation in the MYBPC3 gene, one of the most common causes of HCM. They mixed the sperm with the CRISPR reagents and injected it into eggs from 12 healthy females via intracytoplasmic sperm injection.
The researchers found that just over 70 percent of the 42 CRISPR-injected embryos were successfully edited and contained two normal copies of the MYBPC3 gene. Under normal circumstances, roughly half of the embryos would have the mutation. The gene-corrected embryos developed in a similar manner to control embryos, although they were never intended for implantation.
Interestingly, despite the team introducing a copy of the healthy version of the gene alongside the CRISPR components, they found that the embryos used the maternal copy of the gene as a template for repair instead.
'Our technology successfully repairs the disease-causing gene mutation by taking advantage of a DNA repair response unique to early embryos,' said co-author Dr Jun Wu, at the Salk Institute, California.
Importantly, the scientists used a short-lived version of CRISPR which prevented any further, unwanted editing – known as 'off-target' effects – in the embryos. Injecting CRISPR at the same time as the sperm, instead of shortly after the point of fertilisation when cells are beginning to divide, also meant they avoided previous problems of mosaicism in all but one embryo.
'There is still much to be done to establish the safety of the methods, therefore they should not be adopted clinically,' commented Professor Robin Lovell-Badge of the Francis Crick Institute, who was not involved in the study. He also pointed out that the technique would probably not be able to correct maternal mutations, or even to insert 'more sophisticated genetic alterations.'
'The possibility of producing designer babies, which is unjustified in any case, is now even further away,' he said.
The implantation of edited human embryos is currently illegal in the UK. The HFEA said that high quality public discussion about the ethics of new treatments, expert scientific advice and a robust regulatory system would be crucial if genome editing were to be considered as a new treatment. '[Genome editing] would need to offer new options to couples at risk of having a child with a genetic disease, beyond current treatments like embryo testing,' they said.
Co-author Professor Juan Carlos Izpisua Belmonte of the Salk Institute agreed that scientists will need to proceed with caution as genome editing is still in its infancy.
'Thanks to advances in stem cell technologies and genome editing, we are finally starting to address disease-causing mutations that impact potentially millions of people,' he concluded.
The study was published in the journal Nature.