Well, it was only a matter of time. All the major news outlets are reporting the breakthrough of a research team that managed to use CRISPR/Cas9 to edit human embryos that carried a mutation which causes cardiac hypertrophy (MYBPC3) – a thickening of the heart muscle that is the leading cause of death in young atheletes.
I won’t blog in detail on this, as it’s been covered fairly well by the press (see here or here, or Nature magazine’s own commentary on it here). I do find it slightly ironic that this research was performed in the US which has a ban on public funding into this type of human embryo research – but apparently it’s fine when done with private money! That is not the way to regulate potentially dangerous technologies, folks. These embryos, incidentally, were only allowed to develop for 5 days and not implanted.
There are a few key points about the method that the researchers used [See Figure at the bottom]. Firstly, in order to avoid “off-target” effects, they injected the Cas9 protein itself, bound to its guide RNA, rather than inserting the DNA encoding the CRISPR components into the cells. This was an important safety precaution: the protein degrades much more quickly, which left much less time for it to start snipping DNA where it wasn’t supposed to, essentially. Secondly, they also tried to reduce the risk of making mosaic embryos – ones in which some cells carried the corrected DNA but others still carried the mutation – by injecting these components at the same time as the sperm. Another interesting point is that, as a preliminary test, they generated stem cells from the male patient (induced pluripotent stem cells, to get technical) and tried out the correction on these first – so there’s stem cell technology being used as well. Finally, the process they used was unusually efficient – which will be important if this ever becomes a viable medical technology, otherwise you would require too many embryos. If it ever gets to this stage, and I suspect it will, it’s critically important that rigorous research and testing is done to make sure that it is safe and reliable – not only will a child be born carrying the corrected gene, but this edited gene will be passed on to any future offspring they have themselves.
The most interesting thing to me though was that in fact the embryos did not use the template DNA of the corrected gene that the researchers provide – instead, they were stimulated to use the mother’s DNA, which carried the correct copy of the gene, to repair the mutation carried (in this case) in the father’s sperm. So more research needs to be done as into why this happens. If it is a consistent effect, however, then it essentially eliminates the “designer” baby problem, as the embryo would be using existing human genes to repair faulty ones, and not using artificially engineered DNA to “enhance” already functional genes.
Schematic of MYBPC3∆GAGT gene targeting in MII oocytes. Red indicates the mutant gene, blue the correct gene. In the top row, injection of the CRISPR-Cas9 corrected gene copy occurred after fertilisation, resulting in a high proportion of mosaic embryos carrying some cells with the mutant gene and some with the corrected one. In the bottom row, CRISPR–Cas9 was co-injected with sperm into MII oocytes. This allows genome editing to occur when a sperm contains a single mutant copy and eliminates mosaicism.
Ma, H. et al, Correction of a pathogenic gene mutation in human embryos. Nature (2017) doi:10.1038/nature23305