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Title: Antitumor effects of retargeted AAV2 virus on ovarian cancer in vivo

Hyung Jun Ahn

Korea Institute of Science and Technology, Korea

Biography

Dr. Hyung Jun Ahn is a Principal Research Scientist of Biomedical Research Institute at Korea Institute of Science and Technology (KIST). He received his BS, MS, and PhD degrees from Seoul National University (Chemistry). After postdoctoral training under the supervision of Prof. Yigong Shi at the Department of Molecular Biology, Princeton University, Dr. Ahn joined a Senior Research Scientist, KIST in 2006. Dr. Ahn has been an Adjunct Professor at the Department of Biomedical Engineering in University of Science and Technology since 2010. Dr. Ahn’s research is concerned with biomaterials-based drug delivery, siRNA delivery, and molecular imaging technology.

Abstract

Adeno-associated virus (AAV) is a promising vector for systemic delivery of siRNA due to its long-term expression ability without immunogenicity and pathogenicity. However, its broad host tropism and lack of tissue specificity has limited clinical applications such as cancer therapy. Therefore, redirecting the natural tropism of AAV vectors to unique cell surface antigens is an important requirement for in vivo RNAi-based cancer therapy. To exploit the overexpression property of epithelial cell adhesion molecule (EpCAM) in specific cancer types, we here created anti-EpCAM anitibody-conjugated AAV serotype 2 (AAV2) vectors through a streptavidin-biotin bridge. Upon intravenous injection, anti-EpCAM-conjugated AAV2 vectors showed prominent tumor-specific accumulation in EpCAM-positive tumor-bearing mice without undesirable sequestration in liver. In addition, when loaded with transgenes to express shRNA against epidermal growth factor receptor (EGFR), systemically injected anti-EpCAM-conjugated AAV2/shEGFR vectors induced significant downregulation of EGFR expression in tumors, and eventually suppressed tumor growth even at the long dosing interval of two weeks. This in vivo antitumor effect represents the increased infection efficacy of tropism-modified AAV2 vectors and prolonged expression of EGFR shRNA in tumor tissues. Thus, this study suggests the great potential of anti-EpCAM-conjugated AAV2/shEGFR vectors as RNAi-based cancer therapeutics.
Audience take away:
• We have demonstrated that anti-EpCAM-conjugated AAV2 vectors can be redirected to EpCAM-positive OVCAR3 tumors in vivo without undesirable accumulation in the liver.
• The in vivo antitumor effect represents the increased infection efficacy of tropism-modified AAV2 vectors and prolonged expression of EGFR shRNA in tumor tissues.
• This study suggests the great potential of anti-EpCAM-conjugated AAV2/shEGFR vectors as RNAi-based cancer therapeutics.