Burnett John C, Rossi John J
Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
Chem Biol. 2012 Jan 27;19(1):60-71. doi: 10.1016/j.chembiol.2011.12.008.
Recent advances of biological drugs have broadened the scope of therapeutic targets for a variety of human diseases. This holds true for dozens of RNA-based therapeutics currently under clinical investigation for diseases ranging from genetic disorders to HIV infection to various cancers. These emerging drugs, which include therapeutic ribozymes, aptamers, and small interfering RNAs (siRNAs), demonstrate the unprecedented versatility of RNA. However, RNA is inherently unstable, potentially immunogenic, and typically requires a delivery vehicle for efficient transport to the targeted cells. These issues have hindered the clinical progress of some RNA-based drugs and have contributed to mixed results in clinical testing. Nevertheless, promising results from recent clinical trials suggest that these barriers may be overcome with improved synthetic delivery carriers and chemical modifications of the RNA therapeutics. This review focuses on the clinical results of siRNA, RNA aptamer, and ribozyme therapeutics and the prospects for future successes.
生物药物的最新进展拓宽了各种人类疾病治疗靶点的范围。对于目前正在进行临床研究的数十种基于RNA的疗法来说也是如此，这些疗法用于治疗从遗传疾病到HIV感染再到各种癌症等多种疾病。这些新兴药物，包括治疗性核酶、适配体和小干扰RNA（siRNA），展示了RNA前所未有的多功能性。然而，RNA本质上不稳定，具有潜在免疫原性，并且通常需要载体才能有效转运到靶细胞。这些问题阻碍了一些基于RNA的药物的临床进展，并导致临床试验结果参差不齐。尽管如此，最近临床试验取得的令人鼓舞的结果表明，通过改进合成递送载体和对RNA疗法进行化学修饰，这些障碍可能会被克服。本综述重点关注siRNA、RNA适配体和核酶疗法的临床结果以及未来成功的前景。
