Genetic mutations in viable human embryos have been corrected for the first time using the CRISPR gene editing tool.
Scientists at the Third Affiliated Hospital of Guangzhou Medical University have previously used CRISPR to edit genes of abnormal human embryos, although the success rate was very low. It was hypothesized that this was due to the presence of an extra chromosome. Now the technique has been used on viable human embryos and the results are promising.
To test whether the CRISPR technique could be used to repair genetic defects in viable embryos, the team used immature eggs that had been donated from individuals undergoing IVF treatment.
The team matured the donated eggs and fertilized them using sperm donated from men suffering from hereditary diseases. One sperm donor had an inherited mutation (G1376T) that prevented the synthesis of the G6PD enzyme – a common cause of favism. The second sperm donor had a beta41-42 mutation that caused beta-thalassemia – an inherited blood disease that disrupts synthesis of beta chains of hemoglobin. The CRISPR gene editing tool was introduced into the single-cell embryos prior to cell division.
In one of the studies using abnormal embryos the success rate was one in ten. However, the team found CRISPR to be more effective when editing the genes of viable embryos, although the results were somewhat mixed.
Two embryos had the G1376T mutation corrected although in one case, the gene for the G6PD enzyme was only switched off in some of the cells creating a mosaic embryo.
The CRISPR gene editing tool was less effective at correcting the beta41-42 mutation. Out of four embryos, only one had the mutation corrected in every cell. One of the embryos had the mutation corrected in some cells creating a mosaic embryo, and in two instances CRISPR did not work. The team reports that in one of the embryos, CRISPR had an off-target effect and induced an undesirable mutation, although that mutation was successfully corrected.
The results of the study are promising, but the failure rate is too great for the technique to be used in a clinical setting. In order for that to happen, the scientists would need to further develop their technique to prevent mosaic embryos. One method that may prove effective is to conduct the gene editing on eggs and sperm prior to fertilization.
The researchers’ paper – CRISPR/Cas9-mediated gene editing in human zygotes using Cas9 protein – was recently published in Molecular Genetics and Genomics.