TY - JOUR
T1 - Development and Characterization of a Modular CRISPR and RNA Aptamer Mediated Base Editing System
AU - Collantes, Juan Carlos
AU - Tan, Victor M.
AU - Xu, Huiting
AU - Ruiz-Uriguën, Melany
AU - Alasadi, Amer
AU - Guo, Jingjing
AU - Tao, Hanlin
AU - Su, Chi
AU - Tyc, Katarzyna M.
AU - Selmi, Tommaso
AU - Lambourne, John J.
AU - Harbottle, Jennifer A.
AU - Stombaugh, Jesse
AU - Xing, Jinchuan
AU - Wiggins, Ceri M.
AU - Jin, Shengkan
N1 - Publisher Copyright:
© 2021 Mary Ann Liebert, Inc., publishers.
PY - 2021/2
Y1 - 2021/2
N2 - Conventional CRISPR approaches for precision genome editing rely on the introduction of DNA double-strand breaks (DSB) and activation of homology-directed repair (HDR), which is inherently genotoxic and inefficient in somatic cells. The development of base editing (BE) systems that edit a target base without requiring generation of DSB or HDR offers an alternative. Here, we describe a novel BE system called Pin-pointTM that recruits a DNA base-modifying enzyme through an RNA aptamer within the gRNA molecule. Pin-point is capable of efficiently modifying base pairs in the human genome with precision and low on-target indel formation. This system can potentially be applied for correcting pathogenic mutations, installing premature stop codons in pathological genes, and introducing other types of genetic changes for basic research and therapeutic development.
AB - Conventional CRISPR approaches for precision genome editing rely on the introduction of DNA double-strand breaks (DSB) and activation of homology-directed repair (HDR), which is inherently genotoxic and inefficient in somatic cells. The development of base editing (BE) systems that edit a target base without requiring generation of DSB or HDR offers an alternative. Here, we describe a novel BE system called Pin-pointTM that recruits a DNA base-modifying enzyme through an RNA aptamer within the gRNA molecule. Pin-point is capable of efficiently modifying base pairs in the human genome with precision and low on-target indel formation. This system can potentially be applied for correcting pathogenic mutations, installing premature stop codons in pathological genes, and introducing other types of genetic changes for basic research and therapeutic development.
UR - http://www.scopus.com/inward/record.url?scp=85101551864&partnerID=8YFLogxK
U2 - 10.1089/crispr.2020.0035
DO - 10.1089/crispr.2020.0035
M3 - Artículo
C2 - 33616445
AN - SCOPUS:85101551864
SN - 2573-1599
VL - 4
SP - 58
EP - 68
JO - CRISPR Journal
JF - CRISPR Journal
IS - 1
ER -