Grant: Operating Grant: SickKids-CIHR-IHDCYH New Investigator Grants

<html> <head> </head> <body> <span align="start" style="letter-spacing: normal; text-indent: 0px; text-transform: none; white-space: normal; word-spacing: 0px; display: inline !important; float: none"><font color="rgb(0, 0, 0)" face="Times New Roman" size="medium">The goal of this project is to engineer and apply CRISPR/mini-dSaCas9-VPR-mediated transcriptional activation strategy to restore the expression of the endogenous Shank3 gene and evaluate the rescue of synaptic and neural phenotypes in the InsG3680+/- Shank3 mutant, a mouse model of SHANK3 haploinsufficiency and Autism Spectrum Disorder (ASD). We will further generalize the transcriptional activation strategy by restoring the protein expression and neural function in mutant mouse model of Syngap1+/-, whose mutation causes ASD and childhood brain disorders. By leveraging cutting-edge genetic technologies and advance gene delivery approaches, we will develop and test an innovative platform that allows for correcting impaired neural and behavioral deficits, and identify the developmental time windows enable maximum rescue potential. Our test of this innovative genetic approach in mouse models of ASD, if successful, would hold great potential in clinical translational, and open an avenue for developing effective treatments for ASD or neurodevelopmental disorders caused by SHANK3 and other synaptic gene mutations.</font></span> </body> </html>