小柯机器人

美国加州大学圣迭戈分校Prashant Mali团队利用环形向导RNA招募内源性ADAR实现高效的体外和体内RNA编辑。2022年2月10日，《自然—生物技术》杂志在线发表了这项成果。

Title: Efficient in vitro and in vivo RNA editing via recruitment of endogenous ADARs using circular guide RNAs

Author: Katrekar, Dhruva, Yen, James, Xiang, Yichen, Saha, Anushka, Meluzzi, Dario, Savva, Yiannis, Mali, Prashant

Issue&Volume: 2022-02-10

Abstract: Recruiting endogenous adenosine deaminases using exogenous guide RNAs to edit cellular RNAs is a promising therapeutic strategy, but editing efficiency and durability remain low using current guide RNA designs. In this study, we engineered circular ADAR-recruiting guide RNAs (cadRNAs) to enable more efficient programmable adenosine-to-inosine RNA editing without requiring co-delivery of any exogenous proteins. Using these cadRNAs, we observed robust and durable RNA editing across multiple sites and cell lines, in both untranslated and coding regions of RNAs, and high transcriptome-wide specificity. Additionally, we increased transcript-level specificity for the target adenosine by incorporating interspersed loops in the antisense domains, reducing bystander editing. In vivo delivery of cadRNAs via adeno-associated viruses enabled 53% RNA editing of the mPCSK9 transcript in C57BL/6J mice livers and 12% UAG-to-UGG RNA correction of the amber nonsense mutation in the IDUA-W392X mouse model of mucopolysaccharidosis type I-Hurler syndrome. cadRNAs enable efficient programmable RNA editing in vivo with diverse protein modulation and gene therapeutic applications. Circular guide RNAs boost the efficiency of RNA editing with endogenous ADARs.

DOI: 10.1038/s41587-021-01171-4

Source: https://www.nature.com/articles/s41587-021-01171-4

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
官方网址：https://www.nature.com/nbt/
投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex