Speaker: Chenjie Shen, Ph.D. Affiliation: Postdoctoral Fellow, Guoping Feng Laboratory, McGovern Institute, MIT
Talk title: Advanced Genetic Therapies for the Treatment of Rett Syndrome
Abstract: Despite genome editing technologies have made unprecedented advances during the past decade, therapeutic use of genome editing in the CNS is still in its infancy. Rett syndrome is a neurodevelopmental disorder caused by genetic mutations in a X-linked gene named MECP2. The clinical progression of current gene replacement-based therapies encounters significant challenges owing to the dosage sensitivity of MeCP2. To overcome these challenges and facilitate the translation to human applications, 1). We explored various genetic therapeutic approaches for the most prevalent mutations found in RTT patients, including DNA/RNA base editing and sup-tRNA translational readthrough, aiming to restore MECP2 expression in vivo under its endogenous control. 2). We developed several MeCP2 humanized mouse models and generated iPSCs-derived human neurons to meticulously assess the effectiveness and safety of diverse genetic therapies. 3). We established a highly efficient genome editing method for generating knock in marmoset models that harbor human MeCP2 mutation, which will greatly facilitate study of primate-specific brain mechanisms in Rett Syndrome as well as testing and honing of various genetic therapies for effective genome editing and delivery of genetic medicine.