CRISPR/Cas9-mediated gene editing in human zygotes using Cas9 protein

Mol Genet Genomics. 2017 Jun;292(3):525-533. doi: 10.1007/s00438-017-1299-z. Epub 2017 Mar 1.

Abstract

Previous works using human tripronuclear zygotes suggested that the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system could be a tool in correcting disease-causing mutations. However, whether this system was applicable in normal human (dual pronuclear, 2PN) zygotes was unclear. Here we demonstrate that CRISPR/Cas9 is also effective as a gene-editing tool in human 2PN zygotes. By injection of Cas9 protein complexed with the appropriate sgRNAs and homology donors into one-cell human embryos, we demonstrated efficient homologous recombination-mediated correction of point mutations in HBB and G6PD. However, our results also reveal limitations of this correction procedure and highlight the need for further research.

Keywords: CRISPR/Cas9; Cas9 protein; Gene modification; Homology-directed repair (HDR); Human zygotes.

MeSH terms

  • Base Sequence
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics*
  • Endonucleases / genetics
  • Gene Editing / methods*
  • Genetic Diseases, Inborn / genetics
  • Genetic Diseases, Inborn / therapy*
  • Genome, Human / genetics
  • Glucosephosphate Dehydrogenase / genetics*
  • Homeodomain Proteins / genetics*
  • Humans
  • NIMA-Related Kinase 1 / genetics*
  • Zygote / growth & development*

Substances

  • Homeodomain Proteins
  • RAG-1 protein
  • Glucosephosphate Dehydrogenase
  • NEK1 protein, human
  • NIMA-Related Kinase 1
  • Endonucleases