Modulating CRISPR/Cas9 genome-editing activity by small molecules

Siwei Chen, Deng Chen, Bin Liu, Hidde J Haisma*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

1 Citation (Scopus)
58 Downloads (Pure)

Abstract

Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-mediated genome engineering has become a standard procedure for creating genetic and epigenetic changes of DNA molecules in basic biology, biotechnology, and medicine. However, its versatile applications have been hampered by its overall low precise gene modification efficiency and uncontrollable prolonged Cas9 activity. Therefore, overcoming these problems could broaden the therapeutic use of CRISPR/Cas9-based technologies. Here, we review small molecules with the clinical potential to precisely modulate CRISPR/Cas9-mediated genome-editing activity and discuss their mechanisms of action. Based on these data, we suggest that direct-acting small molecules for Cas9 are more suitable for precisely regulating Cas9 activity. These findings provide useful information for the identification of novel small-molecule enhancers and inhibitors of Cas9 and Cas9-associated endonucleases.

Original languageEnglish
Pages (from-to)951-966
Number of pages16
JournalDrug Discovery Today
Volume27
Issue number4
Early online date22-Nov-2021
DOIs
Publication statusPublished - Apr-2022

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