Substantial collateral effects induced by CasRx in mammalian cells and mice

CRISPR-Cas13 systems have recently been employed to degrade RNA in yeast, plants, mammalian cell lines and animals, however, collateral effects induced by Cas13 may impede their research and therapeutic applications. Here, we found Cas13a and CasRx-mediated RNA knockdown induced substantial collateral effects on both exogenous and endogenous genes in mammalian cells. Moreover, transgenic mice carrying CasRx, with or without targeting guide RNA, exhibited high lethality. Therefore, our results present limitations of CasRx, requiring a solution to address its fidelity before clinical applications.