Development of an mRNA-LNP base editing strategy to activate UBE3A expression in neurons
Development of an mRNA-LNP base editing strategy to activate UBE3A expression in neurons
Base editing is a precision gene-editing approach to make targeted and lasting changes to DNA. This project explores the use of base editing to disrupt the Ube3a antisense transcript (Ube3a-ATS), a mechanism that keeps the Ube3a gene turned off in neurons. The goal of this approach is to increase Ube3a expression in the neurons of the brain. To deliver this to neurons, the system must be packaged inside a carrier, and in this project the carrier is a lipid nanoparticles (LNPs). LNPs have been used successfully in the delivery of therapies like mRNA and can be targeted to different organs in the body by modifying their chemical composition. The goal here is to target the brain through various different modifications to the carrier.
Principle Investigator
Marco Carpenter, PhD
Dr. Marco Carpenter is a researcher at Children's Hospital of Philadelphia specializing in the development of mRNA-LNP technology for pediatric central nervous system diseases. He completed his doctoral training at the University of Pennsylvania under Dr. Elizabeth Heller, where he identified novel molecular targets for brain diseases. His lab is now focused on translating these discoveries into therapeutic applications, leveraging mRNA-LNP delivery platforms to develop precision treatments for children with rare neurological conditions. His current FAST-supported project applies base editing strategies to restore UBE3A expression in neurons — building on his prior success developing LNP approaches for spinal muscular atrophy and alpha-thalassemia — with the goal of creating a one-time gene-editing therapy for pediatric CNS disease.
