Journal Article 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

2017-05-19 , Oxford University Press
ISSN:1362-4962
Description
細胞種に応じてゲノム編集を制御する技術を開発. 京都大学プレスリリース. 2017-05-22.
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.
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http://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/224940/1/nar_gkx309.pdf

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