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

• Published in: BMC cancer Vol. 23; no. 1; pp. 1220 - 9
• Main Authors: Lv, Ya-feng, Zhang, Hao, Cui, Zhi, Ma, Cui-jiao, Li, Yu-ling, Lu, Hua, Wu, Hong-yan, Yang, Jian-lin, Cao, Chun-yu, Sun, Wen-zheng, Huang, Xiao-fei
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.12.2023; BioMed Central; BMC
• Subjects: Adeno-associated viruses; Analysis; Antibodies; Breast Cancer; Cancer; Cancer therapies; Care and treatment; Cell adhesion molecules; DARPins; Diagnosis; Drug dosages; EpCAM; Gene therapy; Gene transfer; Genes; Genetic aspects; Genetic vectors; Health aspects; Patient outcomes; Plasmids; Proteins; Suicide; Suicide genes; Tumors; Vectors (Biology); Viruses; VP2 protein; China; EpCAM; Adeno-associated viruses; Breast Cancer; DARPins
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-023-11705-5

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. 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. The experimental results showed that the AAV2M 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 virus exhibited reduced accumulation in liver tissue and had no impact on tumor growth. This study demonstrates that AAV2M 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.