RNA therapeutics to block USP15-driven neuroinflammation in the brain

Neuroinflammation is a major contributor to the pathogenesis of acute and chronic neurological diseases. This includes diseases such as cerebral malaria, Huntington’s diseases, and amyotrophic lateral sclerosis, and common diseases such as Parkinson’s disease. USP15 is a protein that positively regulates neuroinflammation in the peripheral immune system and in the brain and spinal cord. We have generated potent antisense oligos (ASO) and siRNA that silence USP15 in cell-based assays. The current commercialization priming project aims to test the capacity of these USP15 modalities to block neuroinflammation in vivo following delivery to the brain. Specifically, USP15 inhibitory ASOs and siRNAs produced in our labs will be delivered to the brain using the TERP technology of our industry partner QurCan, and their effect on neuroinflammation will be tested in a mouse model of lethal microbial neuroinflammation.