Gene delivery to breast cancer by incorporated EpCAM targeted DARPins into AAV2

Abstract

Objective: The aim of this study is to evaluate an AAV vector that can selectively target breast cancer cells and to investigate its specificity and anti-tumor effects on breast cancer cells both in vitro and in vivo, offering a new therapeutic approach for the treatment of EpCAM-positive breast cancer.

Methods: In this study, a modified AAV2 viral vector was used, in which EpCAM-specific DARPin EC1 was fused to the VP2 protein of AAV2, creating a viral vector that can target breast cancer cells. The targeting ability and anti-tumor effects of this viral vector were evaluated through in vitro and in vivo experiments.

Results: The experimental results showed that the AAV2M^EC1 virus could specifically infect EpCAM-positive breast cancer cells and accurately deliver the suicide gene HSV-TK to tumor tissue in mice, significantly inhibiting tumor growth. Compared to the traditional AAV2 viral vector, the AAV2M^EC1 virus exhibited reduced accumulation in liver tissue and had no impact on tumor growth.

Conclusion: This study demonstrates that AAV2M^EC1 is a gene delivery vector capable of targeting breast cancer cells and achieving selective targeting in mice. The findings offer a potential gene delivery system and strategies for gene therapy targeting EpCAM-positive breast cancer and other tumor types.

Keywords: Adeno-associated viruses; Breast Cancer; DARPins; EpCAM.