期刊文献+

RNA干扰介导对乙型肝炎病毒复制的抑制作用 被引量:6

原文传递
导出
摘要 构建针对乙型肝炎病毒(HBV)核心区或表面抗原编码区的siRNA表达载体pSI-C和pSI-S,在体外HBV复制细胞模型中观察对HBV复制和表达的影响.将pSI-C,pSI-S与1.3倍HBV真核表达质粒pHBV共转染HepG2细胞,分别在转染后24,48和72h,观察pSI-C和pSI-S对细胞上清和胞内病毒抗原表达的影响,并用分子杂交方法从病毒复制、转录和翻译水平检测目的基因的表达情况.实验结果表明,pSI-C及pSI-S能明显抑制细胞内HBsAg和HBcAg的合成,呈序列特异性和剂量依赖性的特点,而对照组siRNA无抑制作用.pSI-C比pSI-S抑制作用更强,转染后第2天对HBsAg和HBeAg抑制率达高峰,分别为92%和85%.Southern和Northern杂交结果表明,HBVsiRNA能降低目的基因转录和病毒复制中间体的表达水平,提示针对乙型肝炎病毒核心区和表面抗原编码区的siRNA能有效抑制HBVRNA分子转录和病毒复制,最终降低病毒抗原表达,这为运用RNAi技术进行HBV基因治疗提供了新的思路.
出处 《科学通报》 EI CAS CSCD 北大核心 2004年第12期1145-1150,共6页 Chinese Science Bulletin
  • 相关文献

参考文献44

  • 1Will H, Reiser W, Weimer T, et al. Replication strategy of human hepatitis B virus. J Virol, 1987, 61(3): 904~911
  • 2Kao J H, Chen D S. Global control of hepatitis B virus infection.Lancet Infect Dis, 2002, 2:395~403
  • 3Juszczyk J. Clinical course and consequences of hepatitis B infection. Vaccine, 2000, 18(Suppl) 1:S23~25
  • 4Rabe C, Cheng B, Caselmann W H. Molecular mechanisms of hepatitis B virus-associated liver cancer. Dig Dis, 2001, 19(4):279~287
  • 5Yao N, Hong Z, Lau J Y. Application of structural biology tools in the study of viral hepatitis and the design of antiviral therapy.Gastroenterology, 2002, 123(4): 1350~1363
  • 6Niederau C, Heintges T, Lange S, et al. Long-term follow-up of HBeAg-positive patients treated with interferon alpha for chronic hepatitis B. N Engl J Med, 1996, 334(22): 1422~1427
  • 7Mazzella G, Saracco G, Festi D, et al. Long-term results with interferon therapy in chronic type B hepatitis: A prospective randomized trial. Am J Gastroenterol, 1999, 94(8): 2246~2250
  • 8Zoulim F. Therapy of chronic hepatitis B virus infection: Inhibition of the viral polymerase and other antiviral strategies. Antivir Res, 1999, 44(1): 1~30
  • 9Papatheodoridis G V, Dimou E, Papadimitropoulos V. Nucleoside analogues for chronic hepatitis B: Antiviral efficacy and viral resistance. Am J Gastroenterol 2002, 97(7): 1618~1628
  • 10Ayres A, Bartholomeusz A, Lau G, et al. Lamivudine and Famciclovir resistant hepatitis B virus associated with fatal hepatic failure. J Clin Virol, 2003, 27(1 ): 111~116

二级参考文献38

  • 1[1]Geiss G , Jin G, Guo J, et al. A comprehensive view of regulation of gene expression by double-stranded RNA-mediated cell signaling. J Biol Chem, 2001, 276(32): 30178~30182
  • 2[2]Voinnet O, Pinto Y M, Baulcombe D C. Suppression of gene silencing: a general strategy used by diverse DNA and RNA viruses of plants. Proc Natl Acad Sci USA, 1999, 96(24): 14147~14152
  • 3[3]Voinnet O. RNA silencing as a plant immune system against viruses. Trends Genet, 2001, 17(8): 449~459
  • 4[4]Sharp P A. RNAi and double-strand RNA. Genes Dev, 1999, 13(2): 139~141
  • 5[5]Fire A, Xu S, Montgomery M K, et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, 1998, 391(6669): 806~811
  • 6[6]Montgomery M K, Xu S, Fire A. RNA as a target of double-stranded RNA-mediated genetic interference in Caenorhabditis elegans. Proc Natl Acad Sci USA, 1998, 95(26): 15502~15507
  • 7[7]Timmons L, Fire A. Specific interference by ingested dsRNA. Nature, 1998, 395(6705): 854
  • 8[8]Lohmann J U, Endl I, Bosch T C. Silencing of developmental genes in hydra. Dev Biol, 1999, 214(1): 211~214
  • 9[9]Yang D, Lu H, Erickson J W. Evidence that processed small dsRNAs may mediate sequence-specific mRNA degradation during RNAi in Drosophila embryos. Curr Biol, 2000, 10(19): 1191~1200
  • 10[10]Kennerdell J R, Carthew R W. Heritable gene silencing in Drosophila using double-stranded RNA. Nat Biotechnol, 2000, 18(8): 896~898

共引文献25

同被引文献121

引证文献6

二级引证文献27

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部