Step forward for gene editing in human embryos
Scientists from the US, Korea and China have used CRISPR to repair a faulty gene in human embryos. The study is the first to edit genes in human embryos in the US and corrected a mutation in the MYBPC3 gene, which causes heart failure.
Although CRISPR has been used in human embryos before, this is only the second study to use embryos that are, aside from the mutation, genetically normal. The study also shows a marked improvement in both efficiency and safety over the previous studies, which all took place in China. In the study, published in the journal Nature, the researchers used healthy oocytes and sperm from donors that were known to carry a 4 base-pair mutation in the MYBPC3 gene. The CRISPR-Cas9 components were injected into the oocyte together with the sperm in metaphase II. At this stage, there is only one copy of the mutated gene present. The authors hypothesise, therefore, that this measure both increased the chances of repair and reduced the risk of mosaicism, where some cells are repaired, while others still carry the mutation. To further increase both the efficiency and the safety, Cas9 was injected as protein. This is in contrast to some other studies, in which the Cas9 gene is integrated in the genome and would need to be transcribed and translated into protein in order to become active. Previous studies in animals and human cells have shown that injecting Cas9 protein is more efficient than injecting DNA. Furthermore, unlike a Cas9 gene that has been integrated in the DNA, the Cas9 protein used here will disappear from the embryo quickly. It seems likely, then, that the chances of the CRISPR-Cas9 components introducing unwanted, off-target, mutations in the genome are smaller than when using DNA. Interestingly, in most embryos the healthy copy of MYBPC3 from the oocyte, rather than the DNA template that was injected by the researchers, was used to repair the faulty version from the sperm. This was different from other cell types that they and others have studied, and suggests that DNA repair in the early embryo may be different from other cells. It also suggest that in some cases it may not be necessary to inject a template for DNA. This would reduce the number of components that have to be injected into the embryo simultaneously.
The technique used here is potentially applicable to many other diseases. Further studies will be required to determine whether mutations present in the oocytes and/or in genes other than MYBPC3 can be edited as efficiently and safely. It should be noted that editing genes in human embryos is illegal in many countries, including most of Europe, due to fears of introducing unwanted mutations that will be passed on through the generations and lack of consensus over the ethics of human gene editing. While not completely removing safety fears, this study is an important step forward.
One of the study's lead investigators, Juan Carlos Belmonte, will be speaking at the 25th ESGCT Annual Congress in Berlin.
Orignial article: Nature
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