CABE-RY: A PAM-flexible dual-mutation base editor for reliable modeling of multi-nucleotide variants

Multi-nucleotide variants (MNVs) represent an important type of genetic variation and have biological and clinical significance. To simulate MNVs, we designed four dual-mutation base editors combining hA3A(Y130F), TadA8e(V106W), and protospacer adjacent motif (PAM)-flexible SpRY and selected cytosin...

Descripción completa

Detalles Bibliográficos
Autores principales: Tao, Wanyu, Liu, Qing, Huang, Shisheng, Wang, Xin, Qu, Shiyuan, Guo, Junfan, Ou, Danfeng, Li, Guanglei, Zhang, Yu, Xu, Xiangmin, Huang, Xingxu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2021
Materias:
Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413891/
https://www.ncbi.nlm.nih.gov/pubmed/34513298
http://dx.doi.org/10.1016/j.omtn.2021.07.016
Descripción
Sumario:Multi-nucleotide variants (MNVs) represent an important type of genetic variation and have biological and clinical significance. To simulate MNVs, we designed four dual-mutation base editors combining hA3A(Y130F), TadA8e(V106W), and protospacer adjacent motif (PAM)-flexible SpRY and selected cytosine and adenine base editor-SpRY (CABE-RY), which had the best editing performance, for further study. Characterization and comparison showed that CABE-RY had a smaller DNA editing window and lower RNA off-target edits than the corresponding single base editors. Thus, we have established a versatile tool to efficiently simulate MNVs over the genome, which could be very useful for functional studies on MNVs in humans.

Ejemplares similares