Back to Search Start Over

Collateral cleavage of 28s rRNA by RfxCas13d causes death of mice

Authors :
Yunfei Li
Junjie Xu
Xuefei Guo
Zhiwei Li
Lili Cao
Shengde Liu
Ying Guo
Guodong Wang
Yujie Luo
Zeming Zhang
Xuemei Wei
Yingchi Zhao
Tongtong Liu
Xiao Wang
Huawei Xia
Ming Kuang
Qirui Guo
Junhong Li
Luoying Chen
Yibing Wang
Qi Li
Fengchao Wang
Qinghua Liu
Fuping You
Publication Year :
2022
Publisher :
Cold Spring Harbor Laboratory, 2022.

Abstract

SummaryThe CRISPR-Cas13 system is an RNA-guided RNA-targeting system, and has been widely used in transcriptome engineering with potentially important clinical applications. However, it is still controversial whether Cas13 exhibits collateral activity in mammalian cells. Here, we found that knocking down gene expression using RfxCas13d in the adult brain neurons caused death of mice, which was not resulted from the loss of target gene function or off-target effects. Mechanistically, we showed that RfxCas13d exhibited collateral activity in mammalian cells, which is positively correlated with the abundance of target RNA. The collateral activity of RfxCas13d could cleave 28s rRNA into two fragments, leading to translation attenuation and activation of the ZAKα-JNK/p38-immediate early gene (IEG) pathway. These results provide new mechanistic insights into the collateral activity of RfxCas13d and warn that the biosafety of CRISPR-Cas13 system needs further evaluation before applying it to clinical treatments.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........32b04ac38030e5f66e8d8f50e52daa85