Development of a novel RNA-programmable artificial transactivator able to upregulate endogenous genes ad libitum

Abstract

Here we provide a concise overview of a new platform we recently developed for transactivating endogenous genes ad libitum. It relies on a binary design, including an RNA cofactor in charge of recognizing the target gene, and a polypeptidic apofactor stimulating transcription. Compared to similar CRISPR-based devices, our artificial transactivators are seven-folds smaller and elicit a lower, however robust and biologically effective, expression gain. Remarkably, they only work in cells which already transcribe the gene of interest. These properties make our novel platform an appealing potential tool for restoring normal expression levels of haploinsufficient genes upon generalized delivery.