Gene delivery to breast cancer by incorporated EpCAM targeted DARPins into AAV2
Yafeng Lv, Hao Zhang, Zhi Cui, Cui-jiao Ma, Yuling Li, Hua Lu, Hongyan Wu, Jianlin Yang, Chunyu Cao, Wen-Zheng Sun, Xiaofei Huang
Abstract
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.