CRISPR technologies for stem cell engineering and regenerative medicine
2019
Hsu, Mu-Nung | Zhang, Youhan | Truong, Vu Anh | Lai, Po-Liang | Nguyen, Thị Kieu Nuong | Hu, Yu-Chen
CRISPR/Cas9 system exploits the concerted action of Cas9 nuclease and programmable single guide RNA (sgRNA), and has been widely used for genome editing. The Cas9 nuclease activity can be abolished by mutation to yield the catalytically deactivated Cas9 (dCas9). Coupling with the customizable sgRNA for targeting, dCas9 can be fused with transcription repressors to inhibit specific gene expression (CRISPR interference, CRISPRi) or fused with transcription activators to activate the expression of gene of interest (CRISPR activation, CRISPRa). Here we introduce the principles and recent advances of these CRISPR technologies, their delivery vectors and review their applications in stem cell engineering and regenerative medicine. In particular, we focus on in vitro stem cell fate manipulation and in vivo applications such as prevention of retinal and muscular degeneration, neural regeneration, bone regeneration, cartilage tissue engineering, as well as treatment of diseases in blood, skin and liver. Finally, the challenges to translate CRISPR to regenerative medicine and future perspectives are discussed and proposed.
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