An adenovirus-delivered peptide aptamer C1-1 targeting the core protein of hepatitis B virus inhibits viral DNA replication and production in vitro and in vivo

被引:16
作者
Zhang, Wei [1 ]
Ke, Wei [1 ]
Wu, Si-Si [1 ]
Gan, Lu [1 ]
Zhou, Rui [1 ]
Sun, Chang-Yan [1 ]
Long, Qing-Shan [1 ]
Jiang, Wei [1 ]
Xin, Hong-Bo [1 ]
机构
[1] Sichuan Univ, State Key Lab Biotherapy, W China Hosp, Lab Cardiovasc Dis, Chengdu 610041, Peoples R China
基金
中国国家自然科学基金;
关键词
Peptide aptamer; Hepatitis B virus (HBV); Core protein; Adenovirus; LAMIVUDINE; THERAPY;
D O I
10.1016/j.peptides.2009.07.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Peptide aptamers are molecules which can specifically bind to a given target protein and have the potential to selectively block the function of the target protein. It has been reported that a peptide aptamer (C1-1) identified from a randomized expression library specifically bound to the core protein of hepatitis B virus and inhibited viral capsid formation and DNA replication in vitro. Adenoviral systems are popular platforms for reliable gene delivery and high-level transient expression in any mammalian cell type in vitro, and have a natural tropism for the liver after systemic administration. In the present study, we explored the feasibility of gene therapy against HBV infection with adenoviral system, and found that systematic administration of recombinant adenovirus encoding the peptide aptamer (C1-1) significantly inhibited viral capsid formation, HBV DNA replication and virion production in vivo. These results suggest an efficient antiviral treatment against HBV infection by delivery of anti-HBV peptide aptamer with recombinant adenovirus. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:1816 / 1821
页数:6
相关论文
共 19 条
[1]   Identification and characterization of mutations in hepatitis B virus resistant to lamivudine [J].
Allen, MI ;
Deslauriers, M ;
Andrews, CW ;
Tipples, GA ;
Walters, KA ;
Tyrrell, DLJ ;
Brown, N ;
Condreay, LD .
HEPATOLOGY, 1998, 27 (06) :1670-1677
[2]   Current strategies and future directions for eluding adenoviral vector immunity [J].
Bangari, Dinesh S. ;
Mittal, Suresh K. .
CURRENT GENE THERAPY, 2006, 6 (02) :215-226
[3]   Peptide aptamers targeting the hepatitis B virus core protein:: a new class of molecules with antiviral activity [J].
Butz, K ;
Denk, C ;
Fitscher, B ;
Crnkovic-Mertens, I ;
Ullmann, A ;
Schröder, CH ;
Hoppe-Seyler, F .
ONCOGENE, 2001, 20 (45) :6579-6586
[4]   Visualization of a 4-helix bundle in the hepatitis B virus capsid by cryo-electron microscopy [J].
Conway, JF ;
Cheng, N ;
Zlotnick, A ;
Wingfield, PT ;
Stahl, SJ ;
Steven, AC .
NATURE, 1997, 386 (6620) :91-94
[5]  
CROWTHER C, 2008, HUM GENE THER
[6]   3-DIMENSIONAL STRUCTURE OF HEPATITIS-B VIRUS CORE PARTICLES DETERMINED BY ELECTRON CRYOMICROSCOPY [J].
CROWTHER, RA ;
KISELEV, NA ;
BOTTCHER, B ;
BERRIMAN, JA ;
BORISOVA, GP ;
OSE, V ;
PUMPENS, P .
CELL, 1994, 77 (06) :943-950
[7]  
Ding QQ, 2005, MOL CELL, V19, P159, DOI 10.1016/j.molcel.2005.06.009
[8]  
GEYER CY, 2000, CURR PROTOC MOL BIOL, V24, P1
[9]   Transductional targeting of adenovirus vectors for gene therapy [J].
Glasgow, J. N. ;
Everts, M. ;
Curiel, D. T. .
CANCER GENE THERAPY, 2006, 13 (09) :830-844
[10]   A simplified system for generating recombinant adenoviruses [J].
He, TC ;
Zhou, SB ;
da Costa, LT ;
Yu, J ;
Kinzler, KW ;
Vogelstein, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (05) :2509-2514