TY - JOUR
T1 - Next-Generation CRISPR Technologies and Their Applications in Gene and Cell Therapy
AU - Zeballos C., M. Alejandra
AU - Gaj, Thomas
N1 - Funding Information:
M.A.Z.C. was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health ( T32EB019944 ), the Mavis Future Faculty Fellows Program, and by a University of Illinois Aspire Fellowship. This work was also supported by the Muscular Dystrophy Association ( MDA602798 ).
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2021/7
Y1 - 2021/7
N2 - The emergence of clustered regularly interspaced short palindromic repeat (CRISPR) nucleases has transformed biotechnology by providing an easy, efficient, and versatile platform for editing DNA. However, traditional CRISPR-based technologies initiate editing by activating DNA double-strand break (DSB) repair pathways, which can cause adverse effects in cells and restrict certain therapeutic applications of the technology. To this end, several new CRISPR-based modalities have been developed that are capable of catalyzing editing without the requirement for a DSB. Here, we review three of these technologies: base editors, prime editors, and RNA-targeting CRISPR-associated protein (Cas)13 effectors. We discuss their strengths compared to traditional gene-modifying systems, we highlight their emerging therapeutic applications, and we examine challenges facing their safe and effective clinical implementation.
AB - The emergence of clustered regularly interspaced short palindromic repeat (CRISPR) nucleases has transformed biotechnology by providing an easy, efficient, and versatile platform for editing DNA. However, traditional CRISPR-based technologies initiate editing by activating DNA double-strand break (DSB) repair pathways, which can cause adverse effects in cells and restrict certain therapeutic applications of the technology. To this end, several new CRISPR-based modalities have been developed that are capable of catalyzing editing without the requirement for a DSB. Here, we review three of these technologies: base editors, prime editors, and RNA-targeting CRISPR-associated protein (Cas)13 effectors. We discuss their strengths compared to traditional gene-modifying systems, we highlight their emerging therapeutic applications, and we examine challenges facing their safe and effective clinical implementation.
KW - CRISPR
KW - CRISPR-Cas13
KW - base editing
KW - gene therapy
KW - prime editing
UR - http://www.scopus.com/inward/record.url?scp=85097661909&partnerID=8YFLogxK
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U2 - 10.1016/j.tibtech.2020.10.010
DO - 10.1016/j.tibtech.2020.10.010
M3 - Review article
C2 - 33277043
AN - SCOPUS:85097661909
SN - 0167-7799
VL - 39
SP - 692
EP - 705
JO - Trends in Biotechnology
JF - Trends in Biotechnology
IS - 7
ER -