PY4-PUMA

PY4-PUMA is an experimental adenoviral gene therapy designed to selectively target and kill cancer cells harboring RAS mutations, particularly in colorectal and pancreatic cancers. The vector contains the wild-type sequence of the pro-apoptotic protein PUMA (p53 upregulated modulator of apoptosis) driven by a RAS-responsive promoter (PY4). This configuration ensures that PUMA expression is triggered only in cells with high RAS activity. Once expressed, PUMA interacts with and inhibits anti-apoptotic proteins such as Bcl-2 and Bcl-XL, leading to the release of mitochondrial cytochrome C and the induction of apoptosis. Developed by researchers at Tel Aviv Sourasky Medical Center and Tel Aviv University, PY4-PUMA has shown efficacy in preclinical models, including significant inhibition of tumor growth in xenograft studies without apparent toxicity to normal tissues.