Most pills are small molecular inhibitors. In contrast, antibody drugs are large protein molecules that must be administered by injection. Gene editing drugs also are very complicated to deliver.
Small molecular inhibitors are less precise than antibody drugs and gene therapies, but they still have several major advantages. One major advantage of small molecular inhibitors is that they are easier to produce, and they can target many cell types throughout the body very easily. The University of Pennsylvania is working with collaborators to develop inhibitors and PROTACs, which are molecules that can stick to a target protein and cause it to be degraded or destroyed. The goal is to generate a PROTAC drug that will preferentially destroy the mutant form of TREX1. Dr. Nouri Neamati at the University of Michigan is sending compounds to Dr. Miner’s laboratory at the University of Pennsylvania for validation and additional testing. The Miner laboratory has generated multiple model systems for the testing of therapies for RVCL.
PROTACs are small molecule drugs that are designed to interact with a target protein and cause it to be destroyed by the cell’s own machinery. In this case, Dr. Nouri Neamati at the University of Michigan is collaborating with the Miner laboratory at Penn on the development and testing of inhibitors and PROTACs that target TREX1 for the treatment of RVCL.