A reversible RNA on-switch that controls gene expression of AAV-delivered therapeutics in vivo.

ABSTRACT: Widespread use of gene therapy technologies is limited in part by the lack of small genetic switches with wide dynamic ranges that control transgene expression without the requirement of additional protein components^1-5. In this study, we engineered a class of type III hammerhead ribozymes to develop RNA switches that are highly efficient at cis-cleaving mammalian mRNAs and showed that they can be tightly regulated by a steric-blocking antisense oligonucleotide. Our variant ribozymes enabled in vivo regulation of adeno-associated virus (AAV)-delivered transgenes, allowing dose-dependent and up to 223-fold regulation of protein expression over at least 43 weeks. To test the potential of these reversible on-switches in gene therapy for anemia of chronic kidney disease⁶,

SUBMITTER: Zhong G 

PROVIDER: S-EPMC7008088 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature