Correction of a pathogenic gene mutation in human embryos

Gene editing technique successfully corrects mutation in human embryos

image of Correction of a pathogenic gene mutation in human embryos

Researchers in the United States have successfully used a gene editing technique in early stage human embryos to correct a mutation that causes hypertrophic cardiomyopathy.

The embryos in the study were not allowed to develop for more than a few days and were never intended to be implanted into a womb. Further research is needed to establish the safety of the method before it can be adopted clinically. However, if the technique proves to be safe, it could potentially be used for other genetic disorders such as cystic fibrosis or Huntington’s disease.

2017 Study Abstract

Genome editing has potential for the targeted correction of germline mutations. Here we describe the correction of the heterozygous MYBPC3 mutation in human preimplantation embryos with precise CRISPR–Cas9-based targeting accuracy and high homology-directed repair efficiency by activating an endogenous, germline-specific DNA repair response. Induced double-strand breaks (DSBs) at the mutant paternal allele were predominantly repaired using the homologous wild-type maternal gene instead of a synthetic DNA template. By modulating the cell cycle stage at which the DSB was induced, we were able to avoid mosaicism in cleaving embryos and achieve a high yield of homozygous embryos carrying the wild-type MYBPC3 gene without evidence of off-target mutations. The efficiency, accuracy and safety of the approach presented suggest that it has potential to be used for the correction of heritable mutations in human embryos by complementing preimplantation genetic diagnosis. However, much remains to be considered before clinical applications, including the reproducibility of the technique with other heterozygous mutations.

Sources and Press Releases
  • Correction of a pathogenic gene mutation in human embryos, nature, doi:10.1038/nature23305, 02 August 2017.
  • Gene editing technique successfully corrects mutation in human embryos, BMJ 2017;358:j3726, 03 August 2017.
  • Featured image Schematic of MYBPC3∆GAGT gene targeting by injection of CRISPR–Cas9 into human zygotes at the S-phase of the cell cycle. MII oocytes were fertilized by sperm from a heterozygous patient with equal numbers of mutant and wild-type (WT) spermatozoa. CRISPR–Cas9 was then injected into one-cell zygotes. Embryos at the 4–8-cell stage were collected for genetic analysis. Injection during S-phase resulted in mosaic embryos consisting of non-targeted mutant, targeted NHEJ-repaired and targeted HDR-repaired blastomeres. credit nature.
  • Brave New World? Not Even Close, scientificamerican, August 2, 2017.
  • Deadly gene mutations removed from human embryos in landmark study, theguardian, August 2, 2017.
  • Embryo editing technique is ‘ethically dubious’, fertility expert warns, christian, August 8, 2017.

Have your say! Share your views