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

Nucleic Acids Research
Moe HirosawaHirohide Saito

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.

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Citations

Dec 22, 2017·Nature Communications·Nathan H KipnissLei S Qi
Jul 27, 2018·Human Gene Therapy·Shuai Zhen, Xu Li
Jan 30, 2018·Biotechnology Journal·Ricardo Valdés-Bango Curell, Niall Barron
Jan 8, 2019·Developmental Neurobiology·Scott M TaylorPeter F Hitchcock
Apr 16, 2019·Nucleic Acids Research·Mareike D HoffmannDominik Niopek
Jan 21, 2020·Cancer Science·Jiajia LiuXin Jin
Mar 22, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Hua Alexander HanBoon-Seng Soh
Jun 24, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bijay DhungelJason C Steel
May 14, 2020·Advanced Biosystems·Hirohisa OhnoHirohide Saito
Aug 21, 2018·Stem Cells International·Nina XieBeisha Tang
Feb 8, 2019·The Journal of Experimental Biology·Russell C Wyeth
Sep 7, 2018·Harvard Review of Psychiatry·Brian Theyel
Feb 25, 2020·Nucleic Acids Research·Callum J C ParrHirohide Saito
Dec 9, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Chun-Yi YangTzu-Wei Wang
Dec 7, 2017·Cancer Research·Guillermo Aquino-Jarquin
Jan 22, 2019·Molecular Therapy. Nucleic Acids·John LockhartHana Totary-Jain
Jan 13, 2021·Chembiochem : a European Journal of Chemical Biology·Han WuJian-Hui Jiang
Nov 14, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Sean Mc CaffertyNiek N Sanders
Nov 6, 2020·Cell·Daniella McDonaldPrashant Mali
Jul 4, 2019·ACS Synthetic Biology·Moe HirosawaHirohide Saito
Jun 27, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Namita Khajanchi, Krishanu Saha
Sep 29, 2021·The CRISPR Journal·Max van EssenJohn Jacob

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Methods Mentioned

BETA
genetic modifications
transfection
PCR
flow cytometry
fluorescence
gene knockout

Software Mentioned

Excel

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