In vivo genome editing via the HITI method as a tool for gene therapy

J Hum Genet. 2018 Feb;63(2):157-164. doi: 10.1038/s10038-017-0352-4. Epub 2017 Nov 13.


Using genome-editing technologies to correct specific mutations represents a potentially transformative new approach for treating genetic disorders. Despite rapid advances in the field of genome editing, it is still unclear whether the long-standing goal of in vivo targeted transgene integration is feasible. This is primarily because current tools are inefficient. In particular, current technologies are incapable of targeted gene knock-in in non-dividing cells, the major building blocks of adult tissues. This poses a significant barrier for developing therapeutic strategies to treat a broad range of devastating genetic disorders. Recently, our group has developed a unique CRISPR/Cas9-based strategy, termed homology-independent targeted insertion (HITI), which enables targeted gene insertion in non-dividing cells, both in vitro and in vivo. This review will summarize current progress in developing this technology, and discuss the potential impact of HITI-based gene-correction therapies.

Publication types

  • Review

MeSH terms

  • Gene Editing / methods*
  • Genetic Therapy / methods*
  • Genetic Vectors*
  • Humans