Int J Biol Sci 2018; 14(1):57-68. doi:10.7150/ijbs.22235 This issue

Research Paper

Angiotensin 1-7 Overexpression Mediated by a Capsid-optimized AAV8 Vector Leads to Significant Growth Inhibition of Hepatocellular Carcinoma In vivo

Yingying Mao1*, Nana Pei2*, Xinglu Chen3*, Huiying Chen1, Renhe Yan4, Na Bai5, Andrew Li6, Jinlong Li1, Yanling Zhang1, Hongyan Du1, Baihong Chen1, Colin Sumners7, Xuejun Wang8✉, Shengqi Wang8✉, Hongwei Li1✉

1. School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China;
2. Department of Clinical Pathology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China;
3. Clinical Laboratory,The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China;
4. Guangzhou Bioneeds Biotechnology CO., LTD, Guangzhou, Guangdong, China;
5. Deparement of Nuclear Medicine, People's Hospital of Yuxi City, Yuxi, Yunnan, China.
6. Department of Biomedical Engineering, The Johns University School of Medicine, Baltimore, USA;
7. Departments of Physiology and Functional Genomics, University of Florida, Gainesville, Florida, USA.
8. Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, China.
*These authors contributed equally to this work

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
Mao Y, Pei N, Chen X, Chen H, Yan R, Bai N, Li A, Li J, Zhang Y, Du H, Chen B, Sumners C, Wang X, Wang S, Li H. Angiotensin 1-7 Overexpression Mediated by a Capsid-optimized AAV8 Vector Leads to Significant Growth Inhibition of Hepatocellular Carcinoma In vivo. Int J Biol Sci 2018; 14(1):57-68. doi:10.7150/ijbs.22235. Available from

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Graphic abstract

Background: Angiotensin-(1-7) [Ang-(1-7)] has been identified to inhibit the growth of many types of tumor cells both in vitro and in vivo. However, the rapid degradation of Ang-(1-7) in vivo limits its clinical application. Adeno-associated virus (AAV) serotype-8 is a remarkable vector for long-term in vivo gene delivery.

Method: This study was designed to investigate the effects of AAV-mediated Ang-(1-7) overexpression on hepatocellular carcinoma. We first generated three different tyrosine (Y) to phenylalanine (F) mutants of AAV8 (Y447F, Y703F, Y708F) and evaluated their in vivo transduction efficiencies.

Results: The data indicated that the Y703F mutant elicited a significant enhancement of liver gene delivery when compared with wild-type AAV8 (wtAAV8). The anti-tumor effect of Ang-(1-7) mediated by this optimized vector was evaluated in H22 hepatoma-bearing mice. Our results demonstrated that AAV-Ang-(1-7) persistently inhibited the growth of hepatocellular carcinoma by significantly downregulating angiogenesis. This was confirmed by observed decreases in the levels of the proangiogenic factors VEGF and PIGF.

Conclusion: Collectively, these data suggest that Ang-(1-7) overexpression mediated by the optimized vector may be an effective alternative for hepatocellular carcinoma therapy due to its long-term and significant anti-tumor activity.

Keywords: angiotensin-(1-7), hepatocellular carcinoma, adeno-associated virus, gene therapy