Cell-type-specific genome editing with a microRNA-responsive CRISPR-Cas9 switch.

• Hirosawa, Moe

• Fujita, Yoshihiko

• Parr, Callum J C

• Hayashi, Karin

• Kashida, Shunnichi

• Hotta, Akitsu

• Woltjen, Knut

• Saito, Hirohide

Abstract

The CRISPR-Cas9 system is a powerful genome-editing tool useful in a variety of biotechnology and biomedical applications. Here we developed a synthetic RNA-based, microRNA (miRNA)-responsive CRISPR-Cas9 system (miR-Cas9 switch) in which the genome editing activity of Cas9 can be modulated through endogenous miRNA signatures in mammalian cells. We created miR-Cas9 switches by using a miRNA-complementary sequence in the 5΄-UTR of mRNA encoding Streptococcus pyogenes Cas9. The miR-21-Cas9 or miR-302-Cas9 switches selectively and efficiently responded to miR-21-5p in HeLa cells or miR-302a-5p in human induced pluripotent stem cells, and post-transcriptionally attenuated the Cas9 activity only in the target cells. Moreover, the miR-Cas9 switches could differentially control the genome editing by sensing endogenous miRNA activities within a heterogeneous cell population. Our miR-Cas9 switch system provides a promising framework for cell-type selective genome editing and cell engineering based on intracellular miRNA information.

Journal

• Nucleic acids research

  Nucleic acids research 45 (13), e118-e118, 2017-07-27

  Oxford University Press

Keywords

• Genetics

Details

• CRID: 1050845760776773760
• NII Article ID: 120006306001
• ISSN: 13624962
• ISSN: 03051048
• DOI: 10.1093/nar/gkx309
• HANDLE: 2433/224940
• Web Site: http://academic.oup.com/nar/article-pdf/45/13/e118/25367622/gkx309.pdf
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN