A Human Platform to Efficiently Study Class 1 Deleted Genes in Angelman Syndrome

This work will develop a rapid gene insertion platform for human pluripotent stem cell and organoid systems that will unlock the ability to rescue the expression of UBE3A and its ten neighboring protein-coding genes lost in Class 1 deletions. These deleted genes contribute to the clinical phenotypes of AS individuals, and developing an experimental platform that can functionally interrogate and screen for their individual roles and responses to putative therapeutics would be important for over 50-70% of AS individuals with a large 15q11-13 deletion. Human cerebral organoids will also be generated from these stem cell lines to analyze changes in neuronal development, function and responses to putative therapeutics.