Department of Pharmaceutics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, Hunan Province, PR China.
Department of Medicinal Chemistry, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, Hunan Province, PR China.
Int J Biol Macromol. 2019 Jul 1;132:190-202. doi: 10.1016/j.ijbiomac.2019.03.165. Epub 2019 Mar 26.
Identification of biomarkers is essential for diagnosis, targeted therapy and prognosis evaluation of diseases, especially cancers. Currently, the number of ideal clinical biomarkers is still limited partially because of lacking efficient methods in biomarker discovery. Nucleic acid aptamers are artificial single-stranded DNA or RNA sequences that can selectively bind to various targets with high specificity and affinity. Moreover, aptamers possess desirable advantages, including easy synthesis, convenient modification, relative chemical stability and low immunogenicity. Recently, different aptamer-based strategies have been developed to facilitate the discovery of biomarkers. Based on cell-SELEX technology, the selected aptamers can be used to identify cell-surface protein biomarkers of different cancer cells. SOMAscan can analyze thousands of proteins of different biological samples, which becomes a multiplexed protein biomarker discovery platform. Additionally, secreted protein biomarkers can be discovered by aptamers screened through secretome SELEX. In order to facilitate the identification of target proteins, several covalent cross-linking strategies have been developed, such as aptamer-based affinity labeling (ABAL), DNA-templated aptamer and protein-aptamer template (PAT). In this review, we mainly highlight the emerging nucleic acid aptamer-based biomarker discovery strategies and demonstrate their unique technological advantages in discovering cancer biomarkers. The challenges and perspectives of aptamer-based methods are also discussed.
生物标志物的鉴定对于疾病（尤其是癌症）的诊断、靶向治疗和预后评估至关重要。目前，理想的临床生物标志物数量仍然有限，部分原因是缺乏有效的生物标志物发现方法。核酸适体是人工合成的单链 DNA 或 RNA 序列，能够以高特异性和亲和力选择性地结合各种靶标。此外，适体具有理想的优势，包括易于合成、方便修饰、相对化学稳定性和低免疫原性。最近，已经开发了多种基于适体的策略来促进生物标志物的发现。基于细胞 SELEX 技术，筛选出的适体可用于鉴定不同癌细胞的细胞表面蛋白生物标志物。SOMAscan 可以分析数千种不同生物样本的蛋白质，成为一种高通量蛋白质生物标志物发现平台。此外，通过分泌体 SELEX 筛选出的适体可以发现分泌蛋白生物标志物。为了方便靶蛋白的鉴定，已经开发了几种共价交联策略，例如基于适体的亲和标记（ABAL）、DNA 模板适体和蛋白-适体模板（PAT）。在这篇综述中，我们主要强调了新兴的基于核酸适体的生物标志物发现策略，并展示了它们在发现癌症生物标志物方面的独特技术优势。还讨论了基于适体方法的挑战和前景。
