Role of RS-1 derivatives in homology-directed repair at the human genome ATG5 locus

Genome editing is a useful tool in basic and clinical research. Among the several approaches used in genome editing, the CRISPR–Cas9 system using clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) along with a guide RNA has been developed recent...

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Bibliographic Details
Published in:Archives of pharmacal research 2020, 43(6), , pp.639-645
Main Authors: Jeon, In-Sook, Shin, Jae-Cheon, Kim, Seung Ryul, Park, Kwan Sik, Yoo, Hyun Jung, Lee, Kwang Youl, Lee, Hak-Kyo, Choi, Joong-Kook
Format: Article
Language:English
Subjects:
Autophagy-Related Protein 5 - genetics
Benzamides - pharmacology
DNA Breaks, Double-Stranded - drug effects
DNA Repair - drug effects
Gene Editing
HEK293 Cells
HeLa Cells
Humans
Medicine
Pharmacology/Toxicology
Pharmacy
Research Article
Sulfonamides - pharmacology
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Summary:Genome editing is a useful tool in basic and clinical research. Among the several approaches used in genome editing, the CRISPR–Cas9 system using clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) along with a guide RNA has been developed recently. The CRISPR/Cas9 system induces site-specific double-stranded DNA breaks, which result in DNA repair via non-homologous end joining (NHEJ) or homology-directed repair (HDR). However, HDR efficiency is lower than that of NHEJ and accordingly poses a challenge in genome modification studies. Several chemical compounds including RS-1 have been shown to enhance the HDR knock-in process by two- to six-fold in HEK 293 cells and rabbit embryos. Based on this finding, we developed an antibiotic resistance system to screen RS-1 chemical derivatives, which may promote efficient HDR. In this study, we report several chemical compounds with high knock-in efficiency at the ATG5 gene locus, using HeLa cell-based assays.
ISSN:0253-6269
1976-3786
DOI:10.1007/s12272-020-01226-1