Award
National Institute of Mental Health 5R01MH136475-03
CRISPRa-based rescue of sensorimotor deficits in the Scn2a+/- mouse model of autism spectrum disorder
Recipient
University of California, San Francisco
Award Amount
$672,761.00
Ceiling
$672,761.00
Awarded
February 23, 2026
Identifier
5R01MH136475-03
This NIH grant supports research using CRISPRa gene therapy to rescue sensorimotor deficits in a mouse model of autism spectrum disorder caused by SCN2A mutations.
Description
Heterozygous loss-of-function mutations in the sodium channel gene SCN2A are strongly associated with autism spectrum disorder. SCN2A encodes the neuronal sodium channel NaV1.2, which contributes to membrane excitability in somatodendritic or axonal compartments, depending on cell class. Heterozygous loss of Scn2a, modeled in Scn2a+/- mice, causes deficits in cellular excitability and synaptic function across multiple brain areas, and drives robust systems- and behavioral-level deficits in sensory processing, neural coding, and sensorimotor learning. The project aims to rescue these deficits using CRISPR-activation (CRISPRa)-based therapeutic approaches.