Global Science Summit: Pillar 2 Sneak Peek

Dr. Dave Segal, a professor at the University of California, Davis, will highlight two therapeutic approaches designed to “turn on” dad’s UBE3A by targeting the UBE3A-ATS. One approach will feature the implementation of a zinc-finger artificial transcription factor to regulate the expression of UBE3A-ATS while the other will focus on the well-known CRISPR/Cas system that bolsters several mechanisms in which it can target the UBE3A-ATS to allow for dad’s UBE3A expression. Like any therapeutic candidate being developed for AS, a major consideration is not just how the therapy works, but also how it gets to the neurons in the brain where UBE3A is missing. Dr. Segal and his team have been successful in utilizing various viral vectors to package therapeutic candidates targeted to the brain. We look forward to updates on the development of both therapeutic strategies as well as the progress in delivery mechanism for both approaches.

Drs. Yong-Hui Jiang and Jiangbing Zhou from Yale University. Last year we heard about their innovative approach to the delivery of a CRISPR/Cas system to target UBE3A-ATS called Stimuli responsive Traceless Engineering Platform (STEP-RNP) that resulted in promising results in a mouse model of AS including (1) Widespread delivery of the therapeutic candidate throughout the brain, (2) Increased expression of dad’s UBE3A, and (3) behavioral rescue. In utilizing the STEP-RNP platform there are several advantages to the widely used viral vector approach including (1) Overall size of the CRISPR/Cas therapeutic candidate is smaller allowing for easier diffusion across the brain, (2) Avoids capacity limitations of the viral vector, and (3) Sidesteps common viral vector concerns such as immune response and off-target activity. We are excited to hear about all the progress being made with this platform and any updates on the expected timeline for this approach to begin the pre-IND enabling process.

Sirika Pillay, PhD will be presenting an update on ETX-201.

Rebecca Crean, PhD will be presenting an update investigational ASO, ION582.

Kimberly Goodspeed, MD, will be providing an update on investigational ASO, GTX-102.