CRISPR/Cas gene therapy

J Cell Physiol. 2021 Apr;236(4):2459-2481. doi: 10.1002/jcp.30064. Epub 2020 Sep 22.

Abstract

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated enzyme (Cas) is a naturally occurring genome editing tool adopted from the prokaryotic adaptive immune defense system. Currently, CRISPR/Cas9-based genome editing has been becoming one of the most promising tools for treating human genetic diseases, including cardiovascular diseases, neuro-disorders, and cancers. As the quick modification of the CRISPR/Cas9 system, including delivery system, CRISPR/Cas9-based gene therapy has been extensively studied in preclinic and clinic treatments. CRISPR/Cas genome editing is also a robust tool to create animal genetic models for studying and treating human genetic disorders, particularly diseases associated with point mutations. However, significant challenges also remain before CRISPR/Cas technology can be routinely employed in the clinic for treating different genetic diseases, which include toxicity and immune response of treated cells to CRISPR/Cas component, highly throughput delivery method, and potential off-target impact. The off-target effect is one of the major concerns for CRISPR/Cas9 gene therapy, more research should be focused on limiting this impact by designing high specific gRNAs and using high specificity of Cas enzymes. Modifying the CRISPR/Cas9 delivery method not only targets a specific tissue/cell but also potentially limits the off-target impact.

Keywords: CRISPR/Cas9; animal model; gene therapy; genetic disease; genetic disorder; genome editing.

Publication types

  • Review

MeSH terms

  • Animals
  • CRISPR-Associated Protein 9 / genetics*
  • CRISPR-Associated Protein 9 / metabolism
  • CRISPR-Cas Systems*
  • Clustered Regularly Interspaced Short Palindromic Repeats*
  • Disease Models, Animal
  • Gene Editing*
  • Gene Targeting*
  • Genetic Diseases, Inborn / diagnosis
  • Genetic Diseases, Inborn / genetics
  • Genetic Diseases, Inborn / therapy*
  • Genetic Predisposition to Disease
  • Genetic Therapy* / adverse effects
  • Humans
  • Mice, Transgenic

Substances

  • CRISPR-Associated Protein 9