Branch A D
Mount Sinai Medical Center, Division of Liver Diseases and Abdominal Organ Transplantation, New York, NY 10029, USA.
Hepatology. 1996 Dec;24(6):1517-29. doi: 10.1002/hep.510240634.
Antisense pharmaceutical research has sought to provide drugs that would yield effective therapies for diseases resulting from the production of deleterious proteins. The original concept was straightforward: eliminate production of unwanted proteins, such as oncogenic proteins, by blocking the function of their mRNAs; and block their mRNAs by adding "antisense" nucleic acids that bind them through complementary base pairing. However, it has proven difficult to develop clinically useful antisense strategies. Conventional antisense nucleic acids are large, highly charged, complex molecules that interact with a wide variety of unintended cellular and microbial components, often causing "nonantisense effects." It is now clear that a broad knowledge of nucleic acid biochemistry will be needed to optimize antisense molecules for use in patients. The efficacy of naturally occurring antisense molecules and the success of antisense agricultural strategies prove that antisense approaches can be powerful and specific. Pharmaceutical antisense research can be expected to yield many valuable products once sufficient information about antisense mechanisms has been gathered and applied. This article explains the biochemical events that give rise to both antisense and nonantisense effects and provides guidelines for designing and evaluating antisense experiments.
反义药物研究一直致力于提供能有效治疗由有害蛋白质产生所导致疾病的药物。最初的概念很简单：通过阻断致癌蛋白等有害蛋白质的信使核糖核酸（mRNA）的功能来消除其产生；并通过添加能通过互补碱基配对与之结合的“反义”核酸来阻断其mRNA。然而，事实证明，开发临床上有用的反义策略很困难。传统的反义核酸是大的、带高电荷的复杂分子，它们会与各种各样意想不到的细胞和微生物成分相互作用，常常会引起“非反义效应”。现在很清楚，要优化用于患者的反义分子，需要广泛了解核酸生物化学知识。天然存在的反义分子的功效以及反义农业策略的成功证明，反义方法可以强大且具有特异性。一旦收集并应用了足够多关于反义机制的信息，药物反义研究有望产生许多有价值的产品。本文解释了导致反义效应和非反义效应的生化事件，并为设计和评估反义实验提供了指导方针。
