Antisense strategies and therapeutic applications.
Antisense strategies and therapeutic applications.
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反义策略和治疗应用。
DOI：
10.1093/ajhp/53.2.151
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Putnam,DA
中科院分区：
文献类型：
--
作者：
Putnam,DA
讨论了疾病治疗的反义方法的基本概念，并检查了潜在的应用。反义治疗剂结合DNA或RNA序列，以无与伦比的特异性阻断细胞蛋白质的合成。转录和翻译是药物干预的两个过程。反义试剂主要有三大类：反义序列，通常称为反义寡核苷酸；antigene序列;和核酶。反义序列是核酸的衍生物，通过氢键与互补的核酸碱基杂交细胞质信使RNA （mRNA）义链。抗原序列在细胞核中与双链DNA杂交，形成三螺旋。核酶，而不是仅仅通过结合单个目标mRNA来抑制蛋白质合成。将酶促过程与反义iwise配对的特异性结合起来，创造出一种分子，可以使多个目标nirna失能。目前正在体外和体内研究反义治疗剂，用于治疗人类免疫缺陷病毒感染、乙型肝炎病毒感染、单纯疱疹病毒感染、乳头瘤病毒感染、癌症、再狭窄、类风湿性关节炎和过敏性疾病。虽然许多结果是初步的，但有些是有希望的，并已导致临床试验。开发递送反义药物的方法的一个主要目标是降低它们对核酸酶的易感性，同时保持它们与目标位点结合的能力。修饰寡核苷酸中的磷酸二酯键可以在不影响其结合能力的情况下提高序列的酶稳定性。设计用于保护反义结构和改善通过细胞膜的载体系统包括脂质体、水溶性聚合物和纳米颗粒。反义药物的药代动力学正在研究中。反义治疗剂有可能成为药物治疗方案的一个组成部分。
The concepts underlying the antisense approach to disease therapy are discussed, and potential applications are examined.Antisense therapeutic agents bind to DNA or RNA sequences, biocking the synthesis of cellular proteins with unparalleled specificity. Transcription and translation are the two processes with which the agents interfere. There are three major classes of antisense agents: antisense sequences, commonly called antisense oligonucleotides; antigene sequences; and ribozymes. Antisense sequences are derivatives of nucleic acids that hybridize cytosolic messenger RNA (mRNA) sense strands through hydrogen bonding to complementary nucleic acid bases.Antigene sequences hybridize double-stranded DNA in the nucleus, forming triple helixes. Ribozymes, rather than inhibiting protein synthesis simply by binding to a single targeted mRNA. combine enzymatic processes with the specificity of antisense Iwse pairing, creating a molecule that can incapacitate multiple targeted niRNAs. Anti-sense therapeutic agents are being investigated in vitro and in vivo for use in treating human immunodeficiency virus infection, hepatitis B virus infection, herpes simplex virus infection, papillomavirus infection, cancer, restenosis, rheumatoid arthritis, and allergic disorders. Although many results are preliminary, some are promising and has e led to clinical trials. A major goal in developing methods of delivering antisense agents is to reduce their susceptibility to nucleases while retaining their ability to bind to targeted sites. Modification of the phosphodiester linkages in oligonucleotides can lend the sequences enzymatic stability without affecting their binding capacities. Carrier systems designed to protect the antisense structure and improve passage through the cell membrane include liposomes, water-soluble polyrners, and nanoparticles. The pharmacokinetics of anti-sense agents are under investigation.Antisense therapeutic agents have the potential to become an integral part of medicinal regimens.