Verstegen Monique M A, Pan Qiuwei, van der Laan Luc J W
Department of Surgery, Erasmus MC - University Medical Center Rotterdam, Room Na-619,'s, Gravendijkwal 230, 3015CE, Rotterdam, The Netherlands,
Adv Exp Med Biol. 2015;848:1-29. doi: 10.1007/978-1-4939-2432-5_1.
Hepatitis C virus (HCV) is a leading cause of chronic hepatitis and infects approximately three to four million people per year, about 170 million infected people in total, making it one of the major global health problems. In a minority of cases HCV is cleared spontaneously, but in most of the infected individuals infection progresses to a chronic state associated with high risk to develop liver cirrhosis, hepatocellular cancer, or liver failure. The treatment of HCV infection has evolved over the years. Interferon (IFN)-α in combination with ribavirin has been used for decades as standard therapy. More recently, a new standard-of-care treatment has been approved based on a triple combination with either HCV protease inhibitor telaprevir or boceprevir. In addition, various options for all-oral, IFN-free regimens are currently being evaluated. Despite substantial improvement of sustained virological response rates, some intrinsic limitations of these new direct-acting antivirals, including serious side effects, the risk of resistance development and high cost, urge the development of alternative or additional therapeutic strategies. Gene therapy represents a feasible alternative treatment. Small RNA technology, including RNA interference (RNAi) techniques and antisense approaches, is one of the potentially promising ways to investigate viral and host cell factors that are involved in HCV infection and replication. With this, newly developed gene therapy regimens will be provided to treat HCV. In this chapter, a comprehensive overview guides you through the current developments and applications of RNAi and microRNA-based gene therapy strategies in HCV treatment.
丙型肝炎病毒（HCV）是慢性肝炎的主要病因，每年感染约300万至400万人，总计约1.7亿感染者，使其成为全球主要的健康问题之一。在少数情况下，HCV可自发清除，但在大多数感染者中，感染会进展为慢性状态，伴有发展为肝硬化、肝细胞癌或肝衰竭的高风险。多年来，HCV感染的治疗方法不断演变。干扰素（IFN）-α联合利巴韦林已被用作标准疗法数十年。最近，基于与HCV蛋白酶抑制剂特拉匹韦或博赛匹韦的三联组合，一种新的标准治疗方案已获批准。此外，目前正在评估各种全口服、无干扰素治疗方案的选择。尽管持续病毒学应答率有了显著提高，但这些新型直接作用抗病毒药物存在一些内在局限性，包括严重的副作用、耐药性发展风险和高成本，这促使人们开发替代或额外的治疗策略。基因治疗是一种可行的替代治疗方法。小RNA技术，包括RNA干扰（RNAi）技术和反义方法，是研究参与HCV感染和复制的病毒及宿主细胞因子的潜在有前途的方法之一。据此，将提供新开发的基因治疗方案来治疗HCV。在本章中，全面的概述将引导您了解基于RNAi和微小RNA的基因治疗策略在HCV治疗中的当前发展和应用。
