From Mechanisms to Medicine: Viral Gene Regulation as a Platform for Cancer Therapy

 Viruses have evolved highly efficient mechanisms to regulate host cell transcription and establish persistent infection. Our studies of herpesvirus gene regulation have revealed that these viral mechanisms can also provide unexpected opportunities for therapeutic development. In this presentation, I will discuss two complementary approaches that emerged from our studies of virus-host interactions.
 The first approach is based on a short peptide derived from a viral transcriptional regulatory protein. By studying how viral proteins interact with cellular transcriptional machinery, we identified a peptide with the ability to disrupt host transcriptional programs that support cancer cell survival. We are developing this virus-derived peptide as a therapeutic platform and investigating targeted delivery strategies to improve tumor selectivity.
 The second approach takes advantage of disease-specific gene regulation to create a “Trojan Horse” therapeutic strategy. Rather than relying solely on systemic drug activity, we are developing nonviral DNA delivery systems in which regulatory elements selectively activate therapeutic genes in targeted cancer cells. This strategy is being explored initially in virus-associated cancers and is being extended to cancers with defined tumor-specific transcriptional programs.
 Together, these studies illustrate how fundamental investigation of viral gene regulation can provide both therapeutic molecules and new principles for selective drug delivery. By translating mechanisms evolved by viruses into therapeutic tools, we aim to develop treatment strategies that add greater specificity to existing approaches for cancer therapy.