Trepanier Janie B, Tanner Jerome E, Alfieri Caroline
Sainte-Justine Hospital Research Centre, and the Department of Microbiology and Immunology, Université de Montréal, Montréal, Quebec, Canada.
Antivir Ther. 2006;11(3):273-87.
The hepatitis C virus (HCV) is the cause of a silent pandemic that, due to the chronic nature of the disease and the absence of curative therapy, continues to claim an ever-increasing number of lives. Current antiviral regimens have proven largely unsatisfactory for patients with HCV drug-resistant genotypes. It is therefore important to explore alternative therapeutic stratagems whose mode of action allows them to bypass viral resistance. Antisense oligonucleotides, ribozymes, small interfering RNAs, aptamers and deoxyribozymes constitute classes of oligonucleotide-based compounds designed to target highly conserved or functionally crucial regions contained within the HCV genome. The therapeutic expectation for such compounds is the elimination of HCV from infected individuals. Progress in oligonucleotide-based HCV antivirals towards clinical application depends on development of nucleotide designs that bolster efficacy while minimizing toxicity, improvement in liver-targeting delivery systems, and refinement of small-animal models for preclinical testing.
丙型肝炎病毒（HCV）引发了一场隐匿的大流行，由于该疾病的慢性性质以及缺乏治愈性疗法，其导致的死亡人数持续攀升。事实证明，当前的抗病毒治疗方案对于具有HCV耐药基因型的患者在很大程度上并不令人满意。因此，探索替代治疗策略非常重要，这些策略的作用方式能够使其绕过病毒耐药性。反义寡核苷酸、核酶、小干扰RNA、适体和脱氧核酶构成了一类基于寡核苷酸的化合物，旨在靶向HCV基因组中高度保守或功能关键的区域。对这类化合物的治疗期望是从受感染个体中清除HCV。基于寡核苷酸的HCV抗病毒药物在临床应用方面的进展取决于开发既能提高疗效又能将毒性降至最低的核苷酸设计、改进肝脏靶向递送系统以及完善用于临床前测试的小动物模型。
