A new paper in the journal Nature reports the correction of a disease–causing mutation in human embryos. The study is the result of an international collaboration of research centers: the Center for Genome Engineering, within the Institute for Basic Science (IBS, South Korea), Oregon Health and Science University (OHSU, USA), Salk Institute for Biological Studies (USA), BGI–Qingdao and Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics (China).

The scientists used the groundbreaking gene–editing tool CRISPR–Cas9 to repair the DNA piece that causes a common genetic heart disease known as hypertrophic cardiomyopathy. This technique would prevent the disease from being inherited by succeeding generations.

The experiments on the embryos were conducted in the US following all ethical guidelines. IBS researchers provided CRISPR–Cas9 and analyzed the DNA of the embryos to make sure that the procedure worked correctly.

CRISPR–Cas9 combined with in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD) could be helpful for many other genetic diseases. However, the scientists stated that "genome editing approaches must be further optimized" before moving to clinical trials.

"We have succeeded in correcting the mutated gene which causes hypertrophic cardiomyopathy in human embryos with high efficiency and specificity," stresses Jin–Soo Kim, Director of the Center for Genome Engineering, within the Institute for Basic Science (IBS).

Forty percent of all familial hypertrophic cardiomyopathy is caused by a mutation of the MYBPC3 gene on the 11th chromosome. In this study, the researchers dealt with a mutation characterized by four missing base pairs in the MYBPC3 gene. Reintroducing these four base pairs with CRISPR–Cas9 in the embryo prevents this mutation from appearing in future generations.

The experiment on human embryos was conducted by the OHSU research team in the United States. Researchers worked with healthy egg cells, donated by women, and sperm of a man affected by hypertrophic cardiomyopathy.

In this case, CRISPR–Cas9 allowed the correction of the hypertrophic cardiomyopathy mutation carried in the DNA of the sperm. CRISPR–Cas9 works as a pair of genetic scissors designed to cut the DNA near the position of the mutation. Then, the cut is spontaneously repaired by the cell with different mechanisms: one repairs the DNA without leaving any trace, while the other introduces some unwanted insertions or deletions of a few base pairs near the cutting site.

In this study, the researchers injected sperm and CRISPR–Cas9 into the egg at the same time to improve the accuracy of the gene correction. Thanks to this strategy, mosaicism did not occur.

CRISPR–Cas9 cut the DNA at the correct position in all tested embryos (100%) and 42 out of the 58 embryos (72.4%) did not carry the hypertrophic cardiomyopathy mutation. In other words, this technique increased the probability of inheriting the healthy gene from 50% to 72.4%. Moreover, while doing this research the scientists also discovered that human embryos have an alternative DNA repair system, where the Cas9–induced cuts in the DNA coming from the sperm are repaired using the healthy egg's DNA as a template. In the remaining 27.6% embryos, the cellular cut–repairing mechanism introduced some unwanted insertions or deletions near the cut.

Having confirmed that the disease–causing mutation is repaired correctly in human embryos, IBS researchers performed further analysis to make sure that the gene scissors did not cut any other sites of the human genome.