【转移帖】Science：新型MicroRNA肝炎治疗药物
原帖由xuyin发表于 2010-1-6 22:21 ：据12月4日的《科学》杂志报道说，一种针对丙型肝炎的聚焦于可帮助打开和关闭基因的RNA分子的新型治疗策略在黑猩猩中显示了希望。 丙型肝炎是全世界范围内引起肝脏疾病的一个首要原因，受到其感染的人超过1亿7000万，而这些人发生肝衰竭及罹患肝癌的风险会大大地增加。 目前对该病的治疗方案会产生严重的副作用，而且它仅对50%的病例有效。
Robert Lanford及其同僚对一种新的治疗方法进行了研究，这种方法涉及被称作微RNAs的RNA小分子。这些分子是调节范围广泛的细胞过程的关键因子。 丙型肝炎病毒用一种叫做miR-122的微RNA（它在肝脏中有表达）来感染肝脏中的细胞。 在一项对黑猩猩（这是除人之外的唯一能够感染该类型肝炎的动物）的研究中，研究人员应用一种叫做SPC3649的化合物来阻断在4个感染了丙型肝炎病毒的黑猩猩中的miR-122。
文章的作者报告说，该治疗导致了黑猩猩疾病症状的长时间的减少，而且该病毒好像也不会产生抵抗力。
Science December 3, 2009 DOI: 10.1126/science.1178178
Therapeutic Silencing of MicroRNA-122 in Primates with Chronic Hepatitis C Virus Infection
Robert E. Lanford,1,* Elisabeth S. Hildebrandt-Eriksen,2,* Andreas Petri,2,* Robert Persson,2 Morten Lindow,2 Martin E. Munk,2 Sakari Kauppinen,2,3,* Henrik ?rum2,
The liver-expressed microRNA-122 (miR-122) is essential for hepatitis C virus (HCV) RNA accumulation in cultured liver cells, but its potential as a target for antiviral intervention has not been assessed. Here, we show that treatment of chronically infected chimpanzees with a locked nucleic acid (LNA)-modified oligonucleotide (SPC3649) complementary to miR-122 leads to long-lasting suppression of HCV viremia with no evidence for viral resistance or side effects in the treated animals. Furthermore, transcriptome and histological analyses of liver biopsies demonstrated derepression of target mRNAs with miR-122 seed sites, down-regulation of interferon-regulated genes (IRGs), and improvement of HCV-induced liver pathology. The prolonged virological response to SPC3649 treatment without HCV rebound holds promise of a new antiviral therapy with a high barrier to resistance.
1 Department of Virology and Immunology and Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio, TX 78227, USA.
2 Santaris Pharma, Kogle Allé 6, DK-2970 H?rsholm, Denmark.
3 Copenhagen Institute of Technology, Aalborg University, Lautrupvang 15, DK-2750 Ballerup, Denmark.
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