综述与专论: 核酸适配体在分子医学中的应用

分子医学着眼于从疾病的分子层面出发，为个性化精准诊疗提供解决方案。然而，在众多疾病的诊疗中由于缺乏有力的分子识别工具，目前从分子水平上理解和研究疾病仍受到制约。核酸适配体是通过指数富集的配体系统进化（SELEX）技术在体外筛选得到的单链寡核苷酸，具有高选择性、高亲和力、易细胞内化、良好的组织渗透和快速的组织积累能力。近年来，由于其易合成、成本低、稳定性高且免疫原性低，核酸适配体作为分子工具应用于疾病的诊疗一体化受到广泛关注。本综述围绕分子医学中的核酸适配体，讨论了核酸适配体在疾病诊断中的应用，包括基于核酸适配体的肿瘤标志物发现、液体活检、分子成像。介绍了核酸适配体在癌症治疗中的应用包括基于核酸适配体的抑制剂、核酸适配体药物偶联物、纳米药物和核酸适配体介导的免疫治疗。最后对核酸适配体在临床诊疗和产业化面临的问题进行了讨论，包括基于应用场景的筛选方法、核酸适配体与靶标复合物结构、亲和力的机制以及核酸适配体在血液循环中的稳定性等方面。

Review: Applications of Aptamers in Molecular Medicine

Molecular medicine focus on understanding the diseases based on molecular level, and developing personalized medicine strategies for diagnostics and therapeutics. However, powerful molecular recognition tool is still limited for cancer diagnosis and therapy, which impeding cancer research. Aptamers are generated from systematic evolution of ligands by exponential enrichment (SELEX) also known as in vitro selection, ranging from synthetic single-stranded DNA, RNA or XNA (enhanced modified nucleotides), HNA (nucleotides of specific structures such as G quadruplex). The main advantages of aptamers including high specificity, high affinity, simple and rapid synthesis, easy chemical modification, wide target range, good tissue penetration and low immunogenicity. As a molecular recognition tool in molecular medicine, aptamer shows wide applications in developing personalized prediction, diagnosis and therapeutics for its high specificity and high affinity against target. This review discusses the applications of aptamers in disease diagnosis, including aptamer-based tumor marker discovery, liquid biopsy, and molecular imaging, Moreover, the applications of aptamer-based cancer therapy are reviewed, including aptamer-based inhibitors, aptameric drug conjugates, nanomedicines, and aptamer-mediated immunotherapy. Finally, it is promising aptamer will be extensively employed in the future including fundamental research, diagnosis and therapeutics. However, following issues are still need to be addressed. First, the application scenarios-dependent SELEX procedures lack studying which limits the clinical applications of aptamers. Second, the structure of aptamer-target complex has not been fully elucidated, which restricts the precise regulation of aptamers. Third, aptamer is easily degraded by enzymes in vivo and has a short half-life period, which hinders the applications of aptamer-drug conjugates in the development of targeted drugs. With the advancement of screening technology and the further enhancement of aptamer performance, it is expected that aptamers will find more extensive utilization in the field of molecular medicine in the future.