Grant: Project Grant

Oncolytic viruses (OVs) represent a promising therapeutic approach for treating cancer by selectively infecting and destroying tumor cells while sparing normal tissues. Among these, vaccinia virus (VV) stands out due to its ability to deliver therapeutic genes and remodel the tumor microenvironment. However, clinical use of VV faces significant challenges, including off-target effects, limited effectiveness in diverse cancer types, and the time-intensive nature of engineering these large DNA viruses. Traditional methods for creating and optimizing VV candidates can take months, delaying the development of patient-specific or broadly effective therapies. To address these barriers, we have developed a novel strategy leveraging the sensitivity of VV to antibiotics such as puromycin and blasticidin. This approach dramatically accelerates the engineering process by enabling the rapid selection of recombinant viruses with desired traits. By using this tools , we can generate libraries of viruses with targeted mutations in days rather than months. This allows for the systematic identification of genetic changes that enhance VV's ability to target and replicate in cancer cells while minimizing unwanted replication in normal tissues. Ultimately, our goal is to develop a cancer treatment that can destroy tumors, boost the immune system, and improve outcomes for patients with limited treatment options. This work could provide an important new tool in the fight against cancer.