Mitigating off-target effects in CRISPR/Cas9-mediated in vivo gene editing.

Autor: Han HA; Disease Modeling and Therapeutics Laboratory, A*STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore, 138673, Singapore., Pang JKS; Disease Modeling and Therapeutics Laboratory, A*STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore, 138673, Singapore.; Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore, 117543, Singapore., Soh BS; Disease Modeling and Therapeutics Laboratory, A*STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore, 138673, Singapore. bssoh@imcb.a-star.edu.sg.; Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore, 117543, Singapore. bssoh@imcb.a-star.edu.sg.; Key Laboratory for Major Obstetric Disease of Guangdong Province, The Third Affliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China. bssoh@imcb.a-star.edu.sg.
Jazyk: angličtina
Zdroj: Journal of molecular medicine (Berlin, Germany) [J Mol Med (Berl)] 2020 May; Vol. 98 (5), pp. 615-632. Date of Electronic Publication: 2020 Mar 20.
DOI: 10.1007/s00109-020-01893-z
Abstrakt: The rapid advancement of genome editing technologies has opened up new possibilities in the field of medicine. Nuclease-based techniques such as the CRISPR/Cas9 system are now used to target genetically linked disorders that were previously hard-to-treat. The CRISPR/Cas9 gene editing approach wields several advantages over its contemporary editing systems, notably in the ease of component design, implementation and the option of multiplex genome editing. While results from the early phase clinical trials have been encouraging, the small patient population recruited into these trials hinders a conclusive assessment on the safety aspects of the CRISPR/Cas9 therapy. Potential safety concerns include the lack of fidelity in the CRISPR/Cas9 system which may lead to unintended DNA modifications at non-targeted gene loci. This review focuses modifications to the CRISPR/Cas9 components that can mitigate off-target effects in in vitro and preclinical models and its translatability to gene therapy in patient populations.
Databáze: MEDLINE
Externí odkaz: