PERSIST platform provides programmable RNA regulation using CRISPR endoRNases.

ABSTRACT: Regulated transgene expression is an integral component of gene therapies, cell therapies and biomanufacturing. However, transcription factor-based regulation, upon which most applications are based, suffers from complications such as epigenetic silencing that limit expression longevity and reliability. Constitutive transgene transcription paired with post-transcriptional gene regulation could combat silencing, but few such RNA- or protein-level platforms exist. Here we develop an RNA-regulation platform we call "PERSIST" which consists of nine CRISPR-specific endoRNases as RNA-level activators and repressors as well as modular OFF- and ON-switch regulatory motifs. We show that PERSIST-regulated transgenes exhibit strong OFF and ON responses, resist silencing for at least two months, and c

SUBMITTER: DiAndreth B 

PROVIDER: S-EPMC9095627 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature