145
AAV Vectors for Direct Delivery of shRNA into Islet Cells to Treat Pancreatic Cancer
University of Florida
Gene therapy
Oncology
Hit To Lead or Lead Optimization
• shRNA reduces thymidylate synthase (TS) levels, significantly decreasing the progression of pancreatic neuroendocrine tumors (PanNETs).
• This treatment employs an AAV-TS vector that specifically targets pancreatic islet cells. The vector contains small hairpin RNA (shRNA) molecules and releases them into identified pancreatic islet cells.
• This reduces thymidylate synthase (TS) levels, significantly decreasing the progression of pancreatic neuroendocrine tumors (PanNETs). TS acts as a biomarker and therapeutic target.
• Although TS plays a central role in DNA synthesis/repair and is essential for cell proliferation, high levels of TS correlate strongly with tumorigenesis, poor therapeutic outcomes, and low overall survival rates in cancer patients. • A mouse with an hTS/Men1 (-/-) allele established a model to replicate the human disease of PanNET to test how the interfering RNA targeted the TS.
US20190256858A1
Thymidylate synthase accelerates Men1-mediated pancreatic tumor progression and reduces survival. JCI insight, (2022)
