Programmable Transcriptional Modulation with a Structured RNA-Mediated CRISPR-dCas9 Complex

Autor:	Miao He, Xiang Zhou, Zhigang Li, Xue Yin, Wenjie Han, Junxiang Zhou, Xiaoyun Sun, Xiaoyu Liu, Dongbao Yao, Haojun Liang
Rok vydání:	2022
Předmět:	Transcriptional Activation Colloid and Surface Chemistry RNA Clustered Regularly Interspaced Short Palindromic Repeats General Chemistry CRISPR-Cas Systems Biochemistry Catalysis
Zdroj:	Journal of the American Chemical Society. 144:12690-12697
ISSN:	1520-5126 0002-7863
DOI:	10.1021/jacs.2c02271
Popis:	Multi-module dCas9 engineering systems have been developed for controllable transcriptional manipulation such as chemical- or light-induced systems. However, there is still a need for a separate module that can be used for internal control over the CRISPR-dCas9 system. Here, we describe a multi-module CRISPR-dCas9 system in which a separate structured RNA was applied as a programmable component that could control dCas9-based gene regulation and achieved a higher activation efficiency than dCas9-VPR that is traditionally used. By introducing a microRNA sensor, we generated a dCas9-based transcriptional regulation platform that responded to endogenous microRNAs and allowed controllable activation of endogenous genes. Moreover, we applied the platform to selectively identify HCT116 cells in a cell mixture. This work provides a flexible platform for efficient and controllable gene regulation based on CRISPR-dCas9.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b0d08241806e84be9f0a0e3c7fc06263 https://doi.org/10.1021/jacs.2c02271 Zobrazit plný text záznamu