Tools and techniques for the discovery of therapeutic aptamers: recent advances

适体 指数富集配体系统进化 范围(计算机科学) 计算机科学 鉴定(生物学) 风险分析(工程) 计算生物学 生物 医学 遗传学 生物化学 植物 核糖核酸 基因 程序设计语言
作者
Lili Ai,Xinyi Jiang,Kejing Zhang,Cheng Cui,Бо Лю,Weihong Tan
出处
期刊:Expert Opinion on Drug Discovery [Taylor & Francis]
卷期号:18 (12): 1393-1411 被引量:1
标识
DOI:10.1080/17460441.2023.2264187
摘要

ABSTRACTIntroduction The pursuit of novel therapeutic agents for serious diseases such as cancer has been a global endeavor. Aptamers characteristic of high affinity, programmability, low immunogenicity, and rapid permeability hold great promise for the treatment of diseases. Yet obtaining the approval for therapeutic aptamers remains challenging. Consequently, researchers are increasingly devoted to exploring innovative strategies and technologies to advance the development of these therapeutic aptamers.Areas covered The authors provide a comprehensive summary of the recent progress of the SELEX (Systematic Evolution of Ligands by EXponential enrichment) technique, and how the integration of modern tools has facilitated the identification of therapeutic aptamers. Additionally, the engineering of aptamers to enhance their functional attributes, such as inhibiting and targeting, is discussed, demonstrating the potential to broaden their scope of utility.Expert opinion The grand potential of aptamers and the insufficient development of relevant drugs have spurred countless efforts for stimulating their discovery and application in the therapeutic field. While SELEX techniques have undergone significant developments with the aid of advanced analysis instruments and ingeniously updated aptameric engineering strategies, several challenges still impede their clinical translation. A key challenge lies in the insufficient understanding of binding conformation and susceptibility to degradation under physiological conditions. Despite the hurdles, our opinion is optimistic. With continued progress in overcoming these obstacles, the widespread utilization of aptamers for clinical therapy is envisioned to become a reality soon.KEYWORDS: Therapeutic aptamersSELEX techniqueaptamer engineeringprotein degradationreceptor protein blockadetargeted therapy Article highlights The application of aptamers for therapeutic intentions reserves vast potential yet faces the lack of druggable candidates.The optimization of SELEX (Systematic Evolution of Ligands by EXponential enrichment) technique involved varying selection conditions and improving analysis methods, consequently, the promoted efficiency and applicability of SELEX boosted the identification of therapeutic aptamers.The therapeutic potency of aptamers is to some extent impeded by their relatively simple functions and limited working conditions. By leveraging facile engineering methods, aptamers could be endowed with versatile capabilities, such as acting as agonists or antagonists.The utilization of aptamers as targeting segment in therapeutic agents has exhibited promising effects, which facilitates the targeted delivery of chemotherapeutic drugs, nanostructures and immune cells to specific sites within the body.Tools and techniques for understanding the structure–activity relationships (SARs) of aptamers are still in their infancy. Dedicated researchers have the opportunity to drive forward the creation of relevant prediction and analysis approaches, which will undoubtedly aid in unlocking the full potential of aptamers for therapeutic applications.Declaration of interestThe authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Additional informationFundingThis article was supported by the National Key Research and Development Program of China [2021YFA0910000].
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