Heidi Ledford in Nature:
An international team of researchers has used CRISPR–Cas9 gene editing — a technique that allows scientists to make precise changes to genomes with relative ease — to correct a disease-causing mutation in dozens of viable human embryos. The study represents a significant improvement in efficiency and accuracy over previous efforts. The researchers targeted a mutation in a gene called MYBPC3. Such mutations cause the heart muscle to thicken — a condition known as hypertrophic cardiomyopathy that is the leading cause of sudden death in young athletes. The mutation is dominant, meaning that a child need inherit only one copy of the mutated gene to experience its effects. In the gene-editing experiment, published online today in Nature1, the embryos were not destined for implantation. The team also tackled two safety hurdles that had clouded discussions about applying CRISPR–Cas9 to gene therapy in humans: the risk of making additional, unwanted genetic changes (called off-target mutations) and the risk of generating mosaics — in which different cells in the embryo contain different genetic sequences. The researchers say that they have found no evidence of off-target genetic changes, and generated only a single mosaic in an experiment involving 58 embryos.
…Mitalipov’s team took several steps to improve the safety of the technique. The CRISPR system requires an enzyme called Cas9, which cuts the genome at a site targeted by an RNA guide molecule. Typically, researchers wishing to edit a genome will insert DNA encoding CRISPR components into cells, and then rely on the cells' machinery to generate the necessary proteins and RNA. But Mitalipov’s team instead injected the Cas9 protein itself, bound to its guide RNA, directly into the cells.