Regulated control of gene therapies by drug-induced splicing.

ABSTRACT: So far, gene therapies have relied on complex constructs that cannot be finely controlled^1,2. Here we report a universal switch element that enables precise control of gene replacement or gene editing after exposure to a small molecule. The small-molecule inducers are currently in human use, are orally bioavailable when given to animals or humans and can reach both peripheral tissues and the brain. Moreover, the switch system, which we denote X^on, does not require the co-expression of any regulatory proteins. Using X^on, the translation of the desired elements for controlled gene replacement or gene editing machinery occurs after a single oral dose of the inducer, and the robustness of expression can be controlled by the drug dose, protein stability and redo

SUBMITTER: Monteys AM 

PROVIDER: S-EPMC8966400 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature