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

// Guojing Wang 1, 2, 4 , Tingting Jia 5 , Xixia Xu 3 , Le Chang 1, 2, 4 , Rui Zhang 1, 2 , Yu Fu 1, 2, 4 , Yulong Li 1, 2, 4 , Xin Yang 1, 2, 4 , Kuo Zhang 1, 2 , Guigao Lin 1, 2 ,Yanxi Han 1, 2 , Jinming Li 1, 2, 4 1 National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China 2 Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, People’s Republic of China 3 Central Research Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China 4 Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing People’s Republic of China 5 Department 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.