Abstract

Background Ovarian cancer is one of the most aggressive malignancies of the female reproductive system, and the 5-year survival rate is lower than 45%. This study aimed to evaluate a selectively targeted adeno-associated virus (AAV) vector for ovarian cancer, and to investigate its specificity and antitumor efficacy in order to provide experimental evidence for gene therapy of ovarian cancer. Methods The epithelial cell adhesion molecule (EpCAM)-specific binder EC1 was fused into the AAV2 capsid protein VP2 to construct an EpCAM-targeted recombinant vector (AAV2M EC1 ). The targeting and transduction capacity of AAV2M EC1 were assessed in vitro and in vivo . The antitumor effect of AAV2M EC1 was evaluated using the herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) suicide gene system. Results AAV2M EC1 specifically infected ovarian cancer SKOV3 cells and efficiently delivered the HSV-TK gene to tumor tissues. Compared with wild-type AAV2, AAV2M EC1 markedly increased local reporter gene expression in tumors, while reporter gene expression was barely detectable in mouse tissues including the heart, liver, spleen, lung, and kidney. In the presence of GCV, AAV2M EC1 -TK significantly inhibited tumor growth. At the experimental endpoint, tumor volume and tumor weight in the AAV2M EC1 -TK group were reduced by 1.8-fold and 2.3-fold, respectively, compared with those in the AAV2-TK group. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the AAV2M EC1 -TK group were 13.33 U/L and 14.52 U/L, respectively, which were significantly lower than those in the AAV2-TK group (132.92 U/L and 79.09 U/L, respectively) Conclusions AAV2M EC1 is a gene delivery vector with favorable tumor targeting that enables selective in vivo targeting of ovarian cancer, providing experimental support for precision gene therapy in ovarian cancer.