Over half of glioblastoma, a deadly brain cancer, do not express methylguanine methyltransferase (MGMT), an important DNA direct repair enzyme. Tumors lacking MGMT are more sensitive to specific kinds of DNA damage, however, resistance often arises by loss of mismatch repair (MMR), which senses this specific DNA damage and leads to cell death. The Bindra and Herzon Labs developed KL-50 as a novel DNA-damaging agent that is selectively toxic to MGMT-deficient cells regardless of MMR status (Lin and Gueble et al.). Here, we elucidate the mechanism of the molecule in detail and offer chemical explanations for its apparent superiority over a similar DNA-damaging agent, mitozolomide (MTZ). I acted as the cell biology lead on the project.
We used the PONI cationic homopolymer (described below) to deliver plasmid DNA directly to the cytosol, generating an immune response in vitro. Then, we used this system to successfully vaccinate chickens against Newcastle Disease, a lethal viral infection.
