摘要
短单链寡聚核苷酸即核酸适配体,常被称为化学抗体。它们作为传统抗体的替代品,具有显著的优势。这些优势有:高特异性和亲和性,更长的贮存寿命,更简单的工艺,以及更多自由的通过引入化学修饰而对产品进行改进等。通过对一个随机核苷酸序列原始库进行多达10-15次的核酸适配体反复筛选,使它们对靶点具有高亲和性和极高的特异性。基于核酸适配体的检测系统已经被充分研究且有可能代替原始的检测系统。核酸适配体嵌合体(核酸适配体和其他核酸适配体或生物大分子或基团的结合体)具有两个亲代分子的潜在活性,因此具有同时执行不同功能的能力。由于具有极高的特异性且没有免疫原性和病原性,许多其他核酸适配体最近已进入临床试验且获得了制药公司的关注。临床试验的有前途的结果给传统治疗方式带来了新希望。令人鼓舞的临床试验结果给传统治疗方式带来了新希望。与合成药物及其他治疗模式相比,核酸适配体在治疗上的用途已在短期内获得了非常多的关注。这篇文章综合了核酸适配体技术最近在生产,选择,修饰和成功的临床领域等多方面进展。本文着重讲述了主要依靠其选择程序的核酸适配体的多种应用。本文也介绍了各种为提高核酸适配体稳定性和功能而对其进行的各种修饰和嵌合,包括锁核酸(LNAs)的引入。为了强调核酸适配体能够作为高效的诊断剂,我们细致讨论了各种核酸适配体在检测系统中的应用。这篇综述的关键部分主要是基于对多种疾病有良好临床试验疗效的核酸适配体。
关键词: 抗体,核酸适配体,嵌合体,检测,锁核酸(LNA),修饰,SELEX
Current Medicinal Chemistry
Title:Nucleic Acid-Based Aptamers: Applications, Development and Clinical Trials
Volume: 22 Issue: 21
Author(s): Jagat R. Kanwar, Kislay Roy, Nihal G. Maremanda, Krishnakumar Subramanian, Rakesh N. Veedu, Raj Bawa and Rupinder K. Kanwar
Affiliation:
关键词: 抗体,核酸适配体,嵌合体,检测,锁核酸(LNA),修饰,SELEX
摘要: Short single-stranded oligonucleotides called aptamers, often termed as chemical antibodies, have been developed as powerful alternatives to traditional antibodies with respect to their obvious advantages like high specificity and affinity, longer shelf-life, easier manufacturing protocol, freedom to introduce chemical modifications for further improvement, etc. Reiterative selection process of aptamers over 10-15 cycles starting from a large initial pool of random nucleotide sequences renders them with high binding affinity, thereby making them extremely specific for their targets. Aptamer-based detection systems are well investigated and likely to displace primitive detection systems. Aptamer chimeras (combination of aptamers with another aptamer or biomacromolecule or chemical moiety) have the potential activity of both the parent molecules, and thus hold the capability to perform diverse functions at the same time. Owing to their extremely high specificity and lack of immunogenicity or pathogenicity, a number of other aptamers have recently entered clinical trials and have garnered favorable attention from pharmaceutical companies. Promising results from the clinical trials provide new hope to change the conventional style of therapy. Aptamers have attained high therapeutic relevance in a short time as compared to synthetic drugs and/or other modes of therapy. This review follows the various trends in aptamer technology including production, selection, modifications and success in clinical fields. It focusses largely on the various applications of aptamers which mainly depend upon their selection procedures. The review also sheds light on various modifications and chimerizations that have been implemented in order to improve the stability and functioning of the aptamers, including introduction of locked nucleic acids (LNAs). The application of various aptamers in detection systems has been discussed elaborately in order to stress on their role as efficient diagnostic agents. The key aspect of this review is focused on success of aptamers on the basis of their performance in clinical trials for various diseases.
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Cite this article as:
Jagat R. Kanwar, Kislay Roy, Nihal G. Maremanda, Krishnakumar Subramanian, Rakesh N. Veedu, Raj Bawa and Rupinder K. Kanwar , Nucleic Acid-Based Aptamers: Applications, Development and Clinical Trials, Current Medicinal Chemistry 2015; 22 (21) . https://dx.doi.org/10.2174/0929867322666150227144909
DOI https://dx.doi.org/10.2174/0929867322666150227144909 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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