The gene-editing tool CRISPR-Cas9 has incredible promise as a treatment for conditions like HIV and muscular dystrophy, but the ultimate goal would be using it to prevent diseases from taking hold in the first place. That future might be a step closer now, thanks to a pre-clinical trial that has successfully repaired a disease-causing mutation in a human embryo, which would prevent that gene from being passed down to future generations.

CRISPR allows scientists to make extremely targeted edits to the genome of humans, animals and other organisms. Using an enzyme called Cas9, the technique hunts down a specific sequence, say one that causes disease, and snips it out, replacing it with something more benign. While it's attracted its share of controversy, the system has the potential to treat cancer, improve crops and combat antibiotic-resistant bacteria.

The new study focused on a hereditary genetic mutation that can cause hypertrophic cardiomyopathy, a relatively common and potentially life-threatening form of heart disease. The researchers used sperm that was carrying the defective gene, and injected it into a healthy oocyte (egg cell) along with the enzyme that would correct the mutation.

The scientists found that the resulting embryo would patch up the missing gene with a healthy copy from the other parent. Better yet, the process helps avoid another common hurdle with CRISPR editing. When performed at a later stage, some cells carrying the mutation can survive and cause the disease anyway, but by kickstarting the repair process right at the moment of fertilization – when the embryo is only a single cell – the corrected DNA is replicated through every subsequent cell.

Not only would that patient be free of the faulty gene, but all of their offspring would be too, effectively stopping this hereditary disease in its tracks.

"Every generation on would carry this repair because we've removed the disease-causing gene variant from that family's lineage," says Shoukhrat Mitalipov, senior author of the study. "By using this technique, it's possible to reduce the burden of this heritable disease on the family and eventually the human population."

This study was a pre-clinical test designed to examine the technique's safety and effectiveness, and while further optimization is needed before clinical trials can be considered, the results are promising. As the first study to test the method on human eggs, the technique could one day help couples trying to conceive via IVF, particularly those with known genetic conditions who don't want to pass it along to their children.

"This research significantly advances scientific understanding of the procedures that would be necessary to ensure the safety and efficacy of germline gene correction," says Daniel Dorsa, senior vice president for research at Oregon Health and Science University. "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."

The research was published in the journal Nature.

Source: OHSU