Oncotarget

Research Papers:

Novel miR-122 delivery system based on MS2 virus like particle surface displaying cell-penetrating peptide TAT for hepatocellular carcinoma

Guojing Wang _, Tingting Jia, Xixia Xu, Le Chang, Rui Zhang, Yu Fu, Yulong Li, Xin Yang, Kuo Zhang, Guigao Lin, Yanxi Han and Jinming Li

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Oncotarget. 2016; 7:59402-59416. https://doi.org/10.18632/oncotarget.10681

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Abstract

Guojing Wang1,2,4, Tingting Jia5, Xixia Xu3, Le Chang1,2,4, Rui Zhang1,2, Yu Fu1,2,4, Yulong Li1,2,4, Xin Yang1,2,4, Kuo Zhang1,2, Guigao Lin1,2,Yanxi Han1,2, Jinming Li1,2,4

1National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China

2Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, People’s Republic of China

3Central Research Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China

4Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing People’s Republic of China

5Department of Clinical Laboratory, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China

Correspondence to:

Jinming Li, email: jmli@nccl.org.cn

Keywords: MS2 VLP, phage surface display, TAT peptide, miR-122

Received: May 24, 2016    Accepted: July 01, 2016    Published: July 18, 2016

ABSTRACT

Current treatments for hepatocellular carcinoma (HCC) have shown inadequate. MicroRNA-122 (miR-122) mediated RNA interference brings new prospects. A safe, efficient miRNA delivery system is an indispensable assurance. Previously, we developed an MS2 bacteriophage virus-like particle (VLP)-based microRNA delivery system crosslinked with the HIV TAT peptide, which served as an effective inhibitor in the treatments of systemic lupus erythematosus and osteoporosis. However, defects, such as low crosslinking efficiency, high cost, and potential toxicity of the crosslinking agent, needed to be confronted. Therefore, TAT peptide was designed to display on the surface of MS2 VLPs, instead of being chemically crosslinked, using the platform of phage surface display. The results reflected that MS2 VLPs displaying TAT could effectively penetrate the cytomembrane and deliver miR-122. Additionally, its inhibitory effects on HCC were significant in Hep3B, HepG2, and Huh7 cells and Hep3B related animal models. Thus, we have established a novel miR-122 delivery system based on MS2 VLPs surface displaying TAT peptide, which could effectively perform the function of penetrating cytomembrane and the inhibition of HCC.


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