Lönnberg H, Vuorio E
Department of Chemistry Turku University, Finland.
Ann Med. 1996 Dec;28(6):511-22. doi: 10.3109/07853899608999115.
Antisense oligonucleotides represent a novel class of potential drugs for highly selective blocking of genes. The basic concept of antisense strategy is simple: an antisense molecule recognizes a complementary mRNA (or DNA) by sequence-specific base pairing, and hence prevents translation (or transcription), resulting in a selective inhibition of protein synthesis. Because of these properties, antisense oligonucleotides have great potential as therapeutic agents in several human diseases, such as viral diseases, malignancies and dominant hereditary diseases. However, technical difficulties have slowed down their use as drugs: structural modifications are needed to increase the stability and potency of synthetic oligonucleotides, specific delivery systems are required to facilitate their entry into target cells, and more information is needed to their mechanism of action. Much of the current research on antisense oligonucleotides takes place at the interface of chemistry and biomedical sciences, a multidisciplinary field where finding a common language is sometimes difficult. The aim of this review is to present an overview of the antisense strategy in terms which should be understandable for chemists, biologists and physicians.
反义寡核苷酸是一类新型的潜在药物，可用于高度选择性地阻断基因。反义策略的基本概念很简单：反义分子通过序列特异性碱基配对识别互补的信使核糖核酸（mRNA）（或脱氧核糖核酸（DNA）），从而阻止翻译（或转录），导致蛋白质合成的选择性抑制。由于这些特性，反义寡核苷酸在治疗多种人类疾病方面具有巨大潜力，如病毒疾病、恶性肿瘤和显性遗传性疾病。然而，技术难题减缓了它们作为药物的应用：需要进行结构修饰以提高合成寡核苷酸的稳定性和效力，需要特定的递送系统以促进其进入靶细胞，并且需要更多关于其作用机制的信息。目前关于反义寡核苷酸的许多研究都在化学与生物医学科学的交叉领域进行，这是一个多学科领域，有时很难找到共同语言。本综述的目的是以化学家和生物学家以及医生都能理解的术语，对反义策略进行概述。
