CRISPR base editing of cis-regulatory elements enables the perturbation of neurodegeneration-linked genes.

ABSTRACT: CRISPR technology has demonstrated broad utility for controlling target gene expression; however, there remains a need for strategies capable of modulating expression via the precise editing of non-coding regulatory elements. Here, we demonstrate that CRISPR base editors, a class of gene-modifying proteins capable of creating single-base substitutions in DNA, can be used to perturb gene expression via their targeted mutagenesis of cis-acting sequences. Using the promoter region of the human huntingtin (HTT) gene as an initial target, we show that editing of the binding site for the transcription factor NF-κB led to a marked reduction in HTT gene expression in base-edited cell populations. We found that these gene perturbations were persistent and specific, as a transcriptome-wide RNA analy

SUBMITTER: Lim CKW 

PROVIDER: S-EPMC9734028 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature