Genome engineering in human cells

Methods Enzymol. 2014:546:93-118. doi: 10.1016/B978-0-12-801185-0.00005-2.

Abstract

Genome editing in human cells is of great value in research, medicine, and biotechnology. Programmable nucleases including zinc-finger nucleases, transcription activator-like effector nucleases, and RNA-guided engineered nucleases recognize a specific target sequence and make a double-strand break at that site, which can result in gene disruption, gene insertion, gene correction, or chromosomal rearrangements. The target sequence complexities of these programmable nucleases are higher than 3.2 mega base pairs, the size of the haploid human genome. Here, we briefly introduce the structure of the human genome and the characteristics of each programmable nuclease, and review their applications in human cells including pluripotent stem cells. In addition, we discuss various delivery methods for nucleases, programmable nickases, and enrichment of gene-edited human cells, all of which facilitate efficient and precise genome editing in human cells.

Keywords: Disease modeling; Genome editing; Nickases; Pluripotent stem cells; Programmable nuclease; RNA-guided engineered nucleases; Surrogate reporters; Transcription activator-like effector nucleases; Zinc finger nucleases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Deoxyribonucleases / administration & dosage
  • Deoxyribonucleases / genetics
  • Deoxyribonucleases / metabolism
  • Endonucleases / administration & dosage
  • Endonucleases / genetics
  • Endonucleases / metabolism
  • Genetic Engineering / methods*
  • Genetic Therapy
  • Genome, Human*
  • Humans
  • Zinc Fingers

Substances

  • Deoxyribonucleases
  • Endonucleases