SBIR Phase II: Repurposing RNA processing factors to edit RNA for the treatment of Dravet syndrome

This Small Business Innovation Research (SBIR) Phase II project is the development of a safe and effective treatment for a devastating form of pediatric epilepsy called Dravet syndrome. Dravet syndrome is an inherited disease that is caused by mutations. This disease affects children and young adults and results in devastating seizures, developmental issues, and premature death in most patients. Gene therapy is an approach that involves replacement of mutated DNA sequences, but broad use of these approaches has been limited by safety issues. This project follows a unique RNA editing approach to replace defective sequences in the gene in order to halt or reverse the progression of this disease. This project will be instrumental in developing a treatment for nearly 30,000 patients in the U.S. with this condition and would constitute a multibillion-dollar market. This Small Business Innovation Research (SBIR) Phase II project focuses on the development of an RNA editing approach that replaces defective sequences within mutated RNAs as a means to address inherited human disease. The company focuses on Dravet syndrome, a dominantly inherited disease that causes recurrent and devastating seizures in children. Dravet syndrome is caused by mutations in SCN1A, which is an ion channel that is primarily expressed in inhibitory neurons. By targeting defective RNAs with a system that is active only in inhibitory neurons, the company will devise an approach that avoids the risk of toxicities associated with aberrant ion channel expression. Indeed, this disease has resisted gene replacement approaches due to this risk of off-target activities. The company’s system also avoids the use of immunogenic proteins and functions via repurposing of cellular machinery. The result is an inherently non-immunogenic systems which will avoid the varied safety risks associated with use of non-human transcription factor or gene editing systems such as CRISPR (clustered regularly interspaced short palindromic repeats). This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.