Heat-Triggered Remote Control of CRISPR-dCas9 for Tunable Transcriptional Modulation.

ABSTRACT: CRISPR-associated proteins (Cas) are enabling powerful new approaches to control mammalian cell functions, yet the lack of spatially defined, noninvasive modalities limits their use as biological tools. Here, we integrate thermal gene switches with dCas9 complexes to confer remote control of gene activation and suppression with short pulses of heat. Using a thermal switch constructed from the heat shock protein A6 (HSPA6) locus, we show that a single heat pulse 3-5 °C above basal temperature is sufficient to trigger expression of dCas9 complexes. We demonstrate that dCas9 fused to the transcriptional activator VP64 is functional after heat activation, and, depending on the number of heat pulses, drives transcription of endogenous genes GzmB and CCL21 to levels equivalent to t

SUBMITTER: Gamboa L 

PROVIDER: S-EPMC7035993 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature