CRISPR-Cas9 in gene therapy: much control on breaking, little control on repairing
- Published
- Accepted
- Subject Areas
- Cell Biology, Genetics, Molecular Biology
- Keywords
- CRISPR-Cas9, Genome Editing, Gene therapy, DNA repair, Double strand break, homologous recombination, non homologous end joining
- Copyright
- © 2015 Daneshvar
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ PrePrints) and either DOI or URL of the article must be cited.
- Cite this article
- 2015. CRISPR-Cas9 in gene therapy: much control on breaking, little control on repairing. PeerJ PrePrints 3:e818v4 https://doi.org/10.7287/peerj.preprints.818v4
Abstract
Recent advances in CRISPR-Cas9 genome editing tool have made great promises to basic and biomedical research as well as gene therapy. Efforts to make the CRISPR-Cas9 system applicable in gene therapy are largely focused on two aspects: 1) increasing the specificity of this system by eliminating off-target effects, and 2) optimizing in vivo delivery of the CRISPR-Cas9 DNA constructs to target cells and limiting the expression of Cas9 and gRNA to prevent toxicity immune responses. However, there is an unnoted but crucial consideration about the mode of DNA repair at the lesion caused by CRISPR-Cas9. In this commentary, I briefly highlight recent publications on in vivo use of the CRISPR-Cas9 system in gene therapy. I then discuss the undesired on-target DNA repair events that can occur as a result of the activity of CRISPR-Cas9. Overall, this commentary underscores the need for more study on controlled DNA repair in systems targeted with CRISPR-Cas9 genome editing tools.
Author Comment
This version has following updates: 1) Minor text edits, 2) Citations added, 3) Reformatted for better clarity.