TRANSLATION INHIBITORS OF HEPATITIS C VIRUS

这项建议的长期目标是开发有效对抗丙型肝炎病毒(丙型肝炎病毒)的新型抗病毒药物。人类感染丙型肝炎病毒会导致肝脏的进行性破坏，导致肝硬变和肝细胞癌的风险增加。抗病毒药物(如干扰素)在控制丙型肝炎病毒引起的肝病方面成效有限。已经发现了两个新的分子，这两个分子都可以阻止丙型肝炎病毒蛋白的合成，而不会对宿主细胞产生不利影响。这项建议将检查这些分子的直接和脂质体介导的递送单独和组合到实验动物的肝脏。此外，还将测定这些分子在小鼠肝脏和其他各种器官中的分布、稳定性和清除性。如果成功，这些分子阻断丙型肝炎病毒感染的有效性可以在黑猩猩身上进行研究。希望这里提出的实验将导致开发出对人类丙型肝炎病毒感染有效的新型抗病毒药物。建议的商业应用这里提出的实验应该会产生重要的信息，从而开发出对人类丙型肝炎病毒感染有效的新药。

The long term objective of this proposal is to develop novel antiviral drugs effective against hepatitis C virus (HCV). HCV infection in humans leads to progressive destruction of the liver resulting in cirrhosis and heightened risk of hepatocellular carcinoma. Antiviral drugs (such as interferon) have had limited success in controlling HCV-induced liver disease. Two novel molecules have been discovered both of which block HCV protein synthesis without adversely affecting the host cell. This proposal will examine direct and liposome-mediated delivery of these molecules individually and in combination to the liver of experimental animals. In addition, distribution, stability and clearance of these molecules in liver and various other organs of mice will be determined. If successful, the efficacy of these molecules in blocking HCV infection can be studied in chimpanzees. It is hoped that the experiments proposed here will lead to development of novel antiviral drugs effective against HCV infection in humans. PROPOSED COMMERCIAL APPLICATION The experiments proposed here should yield important information leading to development of novel drugs effective against HCV infection in humans.