CRISPR-Cas9 base editors and their current role in human therapeutics

Walker S Lahr; Christopher J Sipe; Joseph G Skeate; Beau R Webber; Branden S Moriarity

doi:10.1016/j.jcyt.2022.11.013

CRISPR-Cas9 base editors and their current role in human therapeutics

Cytotherapy. 2023 Mar;25(3):270-276. doi: 10.1016/j.jcyt.2022.11.013. Epub 2023 Jan 10.

Authors

Walker S Lahr¹, Christopher J Sipe¹, Joseph G Skeate¹, Beau R Webber², Branden S Moriarity³

Affiliations

¹ Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA; Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, USA; Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA.
² Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA; Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, USA.
³ Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA; Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, USA; Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA. Electronic address: mori0164@umn.edu.

Abstract

Background: Consistent progress has been made to create more efficient and useful CRISPR-Cas9-based molecular toolsfor genomic modification.

Methods: This review focuses on recent articles that have employed base editors (BEs) for both clinical and research purposes.

Results: CRISPR-Cas9 BEs are a useful system because of their highefficiency and broad applicability to gene correction and disruption. In addition, base editing has beensuggested as a safer approach than other CRISPR-Cas9-based systems, as it limits double-strand breaksduring multiplex gene knockout and does not require a toxic DNA donor molecule for genetic correction.

Conclusion: As such, numerous industry and academic groups are currently developing base editing strategies withclinical applications in cancer immunotherapy and gene therapy, which this review will discuss, with a focuson current and future applications of in vivo BE delivery.

Keywords: base editor; cancer immunotherapy; gene therapy; hematopoietic stem cell; multiplex gene editing; sickle cell.

Published by Elsevier Inc.

Publication types

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

MeSH terms

CRISPR-Cas Systems* / genetics
DNA
Gene Editing*
Genetic Therapy
Humans

Substances

BES
DNA

Abstract

Publication types

MeSH terms

Substances

Grants and funding