Significance
Adeno-associated virus (AAV) is a promising vector for systemic delivery of siRNA, but its broad host tropism has limited clinical applications. By using the overexpression property of epithelial cell adhesion molecule (EpCAM) on tumors, we demonstrate that anti-EpCAM-conjugated AAV2 vectors through a streptavidin-biotin bridge are redirected to EpCAM-positive tumors in vivo. In addition, when loaded with transgenes to express shRNA against epidermal growth factor receptor (EGFR), systemically injected anti-EpCAM-conjugated AAV2/shEGFR vectors significantly downregulate EGFR expression in tumors, eventually suppressing tumor growth for long periods. We herein suggest the potential of anti-EpCAM-AAV2/shEGFR vectors as an antitumor agent. Furthermore, redirection of AAV2 infection through EpCAM would provide a powerful means for systemic delivery of short hairpin RNA to tumor sites.
Statement of significance
Adeno-associated virus (AAV) is a promising vector for systemic delivery of siRNA, but its broad host tropism has limited clinical applications. By using the overexpression property of epithelial cell adhesion molecule (EpCAM) on tumors, we demonstrate that anti-EpCAM-conjugated AAV2 vectors through a streptavidin-biotin bridge are redirected to EpCAM-positive tumors in vivo. In addition, when loaded with transgenes to express shRNA against epidermal growth factor receptor (EGFR), systemically injected anti-EpCAM-conjugated AAV2/shEGFR vectors significantly downregulate EGFR expression in tumors, eventually suppressing tumor growth for long periods. We herein suggest the potential of anti-EpCAM-AAV2/shEGFR vectors as an antitumor agent. Furthermore, redirection of AAV2 infection through EpCAM would provide a powerful means for systemic delivery of short hairpin RNA to tumor sites.