适配体:一种新的治疗性寡核苷酸

Nrupa G Patel, ipkumar Patel
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摘要

适体是一种寡核苷酸,它是生物核酸(如DNA和RNA)的短版本,具有确定的核苷酸序列。基于分子的复杂性,适体介于蛋白质分子和小化学分子之间。适配体对靶蛋白具有高特异性和亲和力。它们是从随机的寡核苷酸序列中筛选出来的,基于对靶蛋白的最高亲和力,使用SELEX(配体的系统进化指数富集)。研究人员已经发现了适体的各种应用,这些适体已经准备好取代在制造和表征方面具有复杂性的生物蛋白(如抗体)的治疗用途。本文综述了适体的结构修饰,如聚乙二醇化、官能团取代、对映体寡核苷酸的使用及其应用。当需要时,可以通过使用含有与适配体互补的寡核苷酸序列的逆转剂使适配体失活。从安全性的角度来看,适体的这种特性使它们具有潜在的治疗作用。近年来,适体被开发用于靶向药物递送系统,通过与药物分子或递送囊泡(如脂质体)偶联。“反义适配体”正在被开发,以沉默负责癌症组织增殖生长的基因的表达。本文还介绍了适体在环境监测和实验室检测等方面的其他应用。
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Aptamer: A Novel Therapeutic Oligonucleotide
The aptamer is an oligonucleotide which is a short version of biological nucleic acids (such as DNA and RNA) with defined sequence of nucleotides. Based on the complexity of molecule, the aptamers lies in-between protein molecules and small chemical molecules. Aptamers have high specificity and affinity towards target proteins. They are screened from random sequences of oligonucleotides based on the highest affinity for target proteins using the SELEX (Systematic Evolution of Ligands by Exponential Enrichment). Researchers have discovered various applications of aptamers that are ready to replace the therapeutic use of biological proteins (such as antibodies) that have complexity in manufacturing and characterization. The present review describes the structural modification in aptamers such as PEGylation, substitution of functional groups, use of an enantiomeric oligonucleotide and its applications. Aptamers can be deactivated, when needed, by the use of reversal agent that contains oligonucleotide sequence complementary to aptamers. This property of aptamers makes them potential therapeutic from a safety point of view. In recent scenario, aptamers are developed for targeted drug delivery systems by conjugating with drug molecules or delivery vesicles such as liposomes. ‘Anti-sense Aptamers’ are being developed to silent the expression of genes responsible for the proliferative growth of tissue in cancer. Other applications of aptamers such as environmental monitoring and laboratory testing are also described in this review.
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