腺病毒介导的核酶表达消除感染人类肝细胞中的丙型肝炎病毒RNA
Elimination of hepatitis C virus RNA in infected human hepatocytes by adenovirus-mediated expression of ribozymes.
作者信息
Lieber A, He C Y, Polyak S J, Gretch D R, Barr D, Kay M A
机构信息
Department of Medicine, University of Washington, Seattle 98195, USA.
出版信息
J Virol. 1996 Dec;70(12):8782-91. doi: 10.1128/JVI.70.12.8782-8791.1996.
Abstract
Hepatitis C virus (HCV), a positive-strand RNA virus, is the major infectious agent responsible for causing chronic hepatitis. Currently, there is no vaccine for HCV infection, and the only therapy for chronic hepatitis C is largely ineffective. To investigate new genetic approaches to the management of HCV infection, six hammerhead ribozymes directed against a conserved region of the plus strand and minus strand of the HCV genome were isolated from a ribozyme library, characterized, and expressed from recombinant adenovirus vectors. The expressed ribozymes individually or in combination were efficient at reducing or eliminating the respective plus- or minus-strand HCV RNAs expressed in cultured cells and from primary human hepatocytes obtained from chronic HCV-infected patients. This study demonstrates the potential utility of ribozyme therapy as a strategy for the treatment of hepatitis C virus infection.
摘要
丙型肝炎病毒（HCV）是一种正链RNA病毒，是导致慢性肝炎的主要感染因子。目前，尚无针对HCV感染的疫苗，且慢性丙型肝炎的唯一治疗方法在很大程度上效果不佳。为了研究治疗HCV感染的新基因方法，从一个核酶文库中分离出6种针对HCV基因组正链和负链保守区域的锤头状核酶，对其进行了表征，并通过重组腺病毒载体进行表达。所表达的核酶单独或联合使用时，能有效减少或消除在培养细胞以及从慢性HCV感染患者获得的原代人肝细胞中表达的相应正链或负链HCV RNA。本研究证明了核酶疗法作为治疗丙型肝炎病毒感染策略的潜在效用。
相似文献
1
Elimination of hepatitis C virus RNA in infected human hepatocytes by adenovirus-mediated expression of ribozymes.腺病毒介导的核酶表达消除感染人类肝细胞中的丙型肝炎病毒RNA
J Virol. 1996 Dec;70(12):8782-91. doi: 10.1128/JVI.70.12.8782-8791.1996.
2
Ribozyme gene therapy for hepatitis C virus infection.用于丙型肝炎病毒感染的核酶基因治疗。
Clin Diagn Virol. 1998 Jul 15;10(2-3):163-71. doi: 10.1016/s0928-0197(98)00029-4.
3
Hairpin ribozymes in combination with siRNAs against highly conserved hepatitis C virus sequence inhibit RNA replication and protein translation from hepatitis C virus subgenomic replicons.发夹状核酶与针对高度保守的丙型肝炎病毒序列的小干扰RNA相结合，可抑制丙型肝炎病毒亚基因组复制子的RNA复制和蛋白质翻译。
FEBS J. 2005 Nov;272(22):5910-22. doi: 10.1111/j.1742-4658.2005.04986.x.
4
Cleavage of viral RNA and inhibition of viral translation by hepatitis C virus RNA-specific hammerhead ribozyme in vitro.丙型肝炎病毒RNA特异性锤头状核酶在体外对病毒RNA的切割及对病毒翻译的抑制作用
J Hepatol. 1997 Jul;27(1):78-84. doi: 10.1016/s0168-8278(97)80283-8.
5
Intracellular cleavage of hepatitis C virus RNA and inhibition of viral protein translation by hammerhead ribozymes.丙型肝炎病毒RNA的细胞内切割及锤头状核酶对病毒蛋白翻译的抑制作用。
J Clin Invest. 1996 Dec 15;98(12):2720-8. doi: 10.1172/JCI119097.
6
Effective anti-hepatitis B virus hammerhead ribozymes derived from multimeric precursors.源自多聚体前体的有效抗乙型肝炎病毒锤头状核酶
Oligonucleotides. 2007 Spring;17(1):104-12. doi: 10.1089/oli.2006.0049.
7
Investigating a new generation of ribozymes in order to target HCV.研究新一代核酶以针对 HCV 靶点。
PLoS One. 2010 Mar 10;5(3):e9627. doi: 10.1371/journal.pone.0009627.
8
Hepatitis B virus and hepatitis C virus interaction in Huh-7 cells.乙型肝炎病毒和丙型肝炎病毒在 Huh-7 细胞中的相互作用。
J Hepatol. 2009 Sep;51(3):446-57. doi: 10.1016/j.jhep.2009.04.025. Epub 2009 Jun 3.
9
10
Inhibition of hepatitis C virus (HCV)-RNA-dependent translation and replication of a chimeric HCV poliovirus using synthetic stabilized ribozymes.使用合成稳定核酶抑制丙型肝炎病毒（HCV）-RNA依赖性翻译及嵌合HCV脊髓灰质炎病毒的复制。
Hepatology. 2000 Mar;31(3):769-76. doi: 10.1002/hep.510310331.
引用本文的文献
1
Hammerhead Ribozymes: Structural Insights, Catalytic Mechanisms, and Cutting-Edge Applications in Synthetic Biology.锤头状核酶：结构见解、催化机制及合成生物学中的前沿应用
Int J Mol Sci. 2025 Jun 12;26(12):5624. doi: 10.3390/ijms26125624.
2
Development and application of ribonucleic acid therapy strategies against COVID-19.针对 COVID-19 的核糖核酸治疗策略的开发和应用。
Int J Biol Sci. 2022 Aug 1;18(13):5070-5085. doi: 10.7150/ijbs.72706. eCollection 2022.
3
Structural variants and modifications of hammerhead ribozymes targeting influenza A virus conserved structural motifs.靶向甲型流感病毒保守结构基序的锤头状核酶的结构变体与修饰
Mol Ther Nucleic Acids. 2022 May 31;29:64-74. doi: 10.1016/j.omtn.2022.05.035. eCollection 2022 Sep 13.
4
Biochemical features and mutations of key proteins in SARS-CoV-2 and their impacts on RNA therapeutics.SARS-CoV-2 关键蛋白的生化特征和突变及其对 RNA 治疗药物的影响。
Biochem Pharmacol. 2021 Jul;189:114424. doi: 10.1016/j.bcp.2021.114424. Epub 2021 Jan 19.
5
Gene editing and RNAi approaches for COVID-19 diagnostics and therapeutics.基因编辑和 RNAi 方法在 COVID-19 诊断和治疗中的应用。
Gene Ther. 2021 Jun;28(6):290-305. doi: 10.1038/s41434-020-00209-7. Epub 2020 Dec 14.
6
Antiviral Hammerhead Ribozymes Are Effective for Developing Transgenic Suppression of Chikungunya Virus in Aedes aegypti Mosquitoes.抗病毒锤头状核酶对在埃及伊蚊中开发转基因抑制基孔肯雅病毒有效。
Viruses. 2016 Jun 10;8(6):163. doi: 10.3390/v8060163.
7
Design and analysis of hammerhead ribozyme activity against an artificial gene target.针对人工基因靶点的锤头状核酶活性的设计与分析。
Methods Mol Biol. 2014;1103:57-66. doi: 10.1007/978-1-62703-730-3_5.
8
Selective killing of cancer cells by Ashwagandha leaf extract and its component Withanone involves ROS signaling.姜黄属植物叶提取物及其成分 Withanone 通过 ROS 信号选择性杀死癌细胞。
PLoS One. 2010 Oct 21;5(10):e13536. doi: 10.1371/journal.pone.0013536.
9
Effective suppression of Dengue fever virus in mosquito cell cultures using retroviral transduction of hammerhead ribozymes targeting the viral genome.使用针对病毒基因组的锤头状核酶进行逆转录病毒转导，在蚊细胞培养物中有效抑制登革热病毒。
Virol J. 2009 Jun 4;6:73. doi: 10.1186/1743-422X-6-73.
10
Development of lead hammerhead ribozyme candidates against human rod opsin mRNA for retinal degeneration therapy.开发针对人视杆细胞视蛋白mRNA的锤头状核酶候选物用于视网膜变性治疗。
Exp Eye Res. 2009 May;88(5):859-79. doi: 10.1016/j.exer.2008.11.018. Epub 2008 Dec 6.
本文引用的文献
1
Method for multiple portal vein infusions in mice: quantitation of adenovirus-mediated hepatic gene transfer.小鼠多门静脉注射方法：腺病毒介导的肝脏基因转移定量分析
Biotechniques. 1996 Feb;20(2):278-85. doi: 10.2144/96202rr05.
2
Adenovirus-mediated expression of ribozymes in mice.腺病毒介导的核酶在小鼠中的表达。
J Virol. 1996 May;70(5):3153-8. doi: 10.1128/JVI.70.5.3153-3158.1996.
3
Stable high-level gene expression in mammalian cells by T7 phage RNA polymerase.利用T7噬菌体RNA聚合酶在哺乳动物细胞中实现稳定的高水平基因表达。
Methods Enzymol. 1993;217:47-66. doi: 10.1016/0076-6879(93)17055-a.
4
Correlation between the infectivity of hepatitis C virus in vivo and its infectivity in vitro.丙型肝炎病毒体内感染性与其体外感染性之间的相关性。
Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6037-41. doi: 10.1073/pnas.90.13.6037.
5
Detection of genomic and intermediate replicative strands of hepatitis C virus in liver tissue by in situ hybridization.通过原位杂交检测肝组织中丙型肝炎病毒的基因组和中间复制链。
J Clin Invest. 1993 May;91(5):2226-34. doi: 10.1172/JCI116449.
6
A mutant T7 phage promoter is specifically transcribed by T7-RNA polymerase in mammalian cells.一种突变型T7噬菌体启动子在哺乳动物细胞中被T7-RNA聚合酶特异性转录。
Eur J Biochem. 1993 Oct 1;217(1):387-94. doi: 10.1111/j.1432-1033.1993.tb18257.x.
7
8
Development of ribozymes for gene therapy.用于基因治疗的核酶的开发。
J Invest Dermatol. 1994 Nov;103(5 Suppl):85S-89S. doi: 10.1038/jid.1994.15.
9
10
Antiviral and anticancer ribozymes.抗病毒和抗癌核酶。
Curr Opin Oncol. 1994 Nov;6(6):601-6. doi: 10.1097/00001622-199411000-00012.
Zotero 插件