Date: Friday, April 22, 2022
Time: 12:00pm – 1:00pm
Location: Zoom meeting – https://mit.zoom.us/j/97743148391
Speaker: Chenjie Shen, Ph.D.
Affiliation: Simons Fellow, Guoping Feng Laboratory, McGovern Institute, MIT
Talk title: From Disease Modeling to Next-Generation Gene Therapy
Abstract: Heterozygous mutations in the X-linked MeCP2 gene cause the profound neurological disorder Rett syndrome (RTT). Currently, there are no FDA-approved medicines for RTT. The traditional RTT gene therapy approach based on gene replacement faces two key challenges in preclinical development: First, MeCP2 is dosage-sensitive, and its overexpression causes MeCP2 duplication syndrome. Therefore, the level of MeCP2 in each cell must be maintained within physiological limits. In addition, due to X chromosome inactivation, gene therapy in RTT females has to accommodate the fact that approximately 50% of cells are already expressing wild-type MeCP2. Our research focuses on developing the next-generation gene therapy approaches including RNA and DNA base editing to restore MeCP2 function under its endogenous regulation. Besides, we develop a high efficacy of genome editing method for generating the MeCP2 knock-in marmoset model that is promising for both mechanistic and translational studies.