RAAV-CRISPRa therapy corrects Rai1 haploinsufficiency and rescues selective disease features in Smith-Magenis syndrome mice.

ABSTRACT: Haploinsufficiency in retinoic acid induced 1 (RAI1) causes Smith-Magenis syndrome (SMS), a severe neurodevelopmental disorder characterized by neurocognitive deficits and obesity. Currently, curative treatments for SMS do not exist. Here, we take a recombinant adeno-associated virus (rAAV)-clustered regularly interspaced short palindromic repeats activation (CRISPRa) approach to increase expression of the remaining intact Rai1 allele. Building upon our previous work that found the paraventricular nucleus of hypothalamus plays a central role in SMS pathogenesis, we performed paraventricular nucleus of hypothalamus-specific rAAV-CRISPRa therapy by increasing endogenous Rai1 expression in SMS (Rai1^±) mice. We found that rAAV-CRISPRa therapy rescues excessive repetitive behavior, d

SUBMITTER: Chang HC 

PROVIDER: S-EPMC9762195 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature