Delivery Approaches for Therapeutic Genome Editing and Challenges

Genes (Basel). 2020 Sep 23;11(10):1113. doi: 10.3390/genes11101113.


Impressive therapeutic advances have been possible through the advent of zinc-finger nucleases and transcription activator-like effector nucleases. However, discovery of the more efficient and highly tailorable clustered regularly interspaced short palindromic repeats (CRISPR) and associated proteins (Cas9) has provided unprecedented gene-editing capabilities for treatment of various inherited and acquired diseases. Despite recent clinical trials, a major barrier for therapeutic gene editing is the absence of safe and effective methods for local and systemic delivery of gene-editing reagents. In this review, we elaborate on the challenges and provide practical considerations for improving gene editing. Specifically, we highlight issues associated with delivery of gene-editing tools into clinically relevant cells.

Keywords: CRISPR-Cas; TALENs; ZFNs; base editors; delivery methods; gene editing; nonviral delivery; viral delivery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • CRISPR-Cas Systems*
  • Gene Editing*
  • Gene Transfer Techniques / standards*
  • Genetic Therapy*
  • Genetic Vectors / administration & dosage*
  • Humans