Injectable protein gene activation therapy for PWS (year 2)

This proposal will investigate the development of a gene therapy for Prader-Willi syndrome (PWS). PWS is caused by the loss of a region of human chromosome 15q11-13. Humans have two copies of chromosome 15, one the mother (maternal) and one from the father (paternal). Due to an unusual mechanism called genetic imprinting, the genes affecting PWS are active only on the paternal chromosome. Therefore if these genes get deleted from the paternal chromosome, there are no active copies of these genes remaining in the brain. The genes are intact on the maternal chromosome, but are not active. Here we propose a way to activate the genes on the maternal chromosome. My lab has actually been engineering special proteins designed to turn off these genes, as a method to treat a related disorder called Angelman syndrome. However, by reconfiguring these proteins to activate the genes rather than repress them, we hypothesize that we can activate the inactive but otherwise normal genes on the maternal chromosome. We will test this hypothesis in mouse models of PWS. If successful, this could represent an important first step towards a gene therapy to treat the underlying cause of PWS.

This project is in honor of Olivia Viroslav.