A deep screen of RNA-based therapeutics for STXBP1 syndrome
Awardee: Chaolin Zhang
Institution: The Trustees of Columbia University in the City of New York
Grant Amount: $69,708
Funding Period: February 1, 2025 - January 31, 2026
Summary:
This project, led by Chaolin Zhang at Columbia University, aims to develop a new treatment for STXBP1 syndrome, a severe genetic disorder linked to epilepsy. The research focuses on using RNA-based therapeutics, specifically antisense oligonucleotides (ASOs), to boost the production of the STXBP1 protein, which is deficient in patients with the syndrome. ASOs have already shown promise in treating other genetic disorders, such as spinal muscular atrophy. The challenge lies in identifying the most effective RNA regions to target with ASOs. Zhang’s team has developed a high-throughput screening method using a modified CRISPR/Cas13 system, which can help pinpoint these key regions in the STXBP1 gene’s untranslated regions (UTRs). By applying this method, they hope to identify RNA elements that regulate the gene’s stability and protein production. Once identified, these elements will be validated using ASOs in human cell models to confirm their ability to restore STXBP1 protein production. If successful, this research could pave the way for a targeted treatment for STXBP1 syndrome and provide a model for developing therapies for other genetic disorders.