Reducing off target viral delivery in ovarian cancer gene therapy using a protease-activated AAV2 vector platform.

ABSTRACT: Gene therapy is a promising strategy for treating metastatic epithelial ovarian cancer (EOC). However, efficient vector targeting to tumors is difficult and off-target effects can be severely detrimental. Most vector targeting approaches rely on surface receptors overexpressed on some subpopulation of cancer cells. Unfortunately, there is no universally expressed cell surface biomarker for tumor cells. As an alternative, we developed an adeno-associated virus (AAV) based "Provector" whose cellular transduction can be activated by extracellular proteases, such as matrix metalloproteinases (MMP) that are overexpressed in the tumor microenvironments of the most aggressive forms of EOC. In a non-tumor bearing mouse model, the Provector demonstrates efficient de-targeting of healthy tissues, es

SUBMITTER: Tong JG 

PROVIDER: S-EPMC7428868 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature