Delivery and therapeutic applications of gene editing technologies ZFNs, TALENs, and CRISPR/Cas9

Int J Pharm. 2015 Oct 15;494(1):180-94. doi: 10.1016/j.ijpharm.2015.08.029. Epub 2015 Aug 13.

Abstract

In recent years, several new genome editing technologies have been developed. Of these the zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the CRISPR/Cas9 RNA-guided endonuclease system are the most widely described. Each of these technologies utilizes restriction enzymes to introduce a DNA double stranded break at a targeted location with the guide of homologous binding proteins or RNA. Such targeting is viewed as a significant advancement compared to current gene therapy methods that lack such specificity. Proof-of-concept studies have been performed to treat multiple disorders, including in vivo experiments in mammals and even early phase human trials. Careful consideration and investigation of delivery strategies will be required so that the therapeutic potential for gene editing is achieved. In this review, the mechanisms of each of these gene editing technologies and evidence of therapeutic potential will be briefly described and a comprehensive list of past studies will be provided. The pharmaceutical approaches of each of these technologies are discussed along with the current delivery obstacles. The topics and information reviewed herein provide an outline of the groundbreaking research that is being performed, but also highlights the potential for progress yet to be made using these gene editing technologies.

Keywords: CRISPR/Cas9; Gene editing; Non-viral vectors; Transcription activator-like effector nucleases; Viral vectors; Zinc finger nucleases.

Publication types

  • Review

MeSH terms

  • Animals
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics*
  • DNA / genetics
  • Deoxyribonucleases / genetics*
  • Endodeoxyribonucleases / genetics*
  • Genetic Therapy / methods
  • Humans
  • RNA / genetics
  • RNA Editing / genetics*
  • Zinc Fingers / genetics*

Substances

  • RNA
  • DNA
  • Deoxyribonucleases
  • Endodeoxyribonucleases