The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, Zhejiang325027, China.
Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang325000, China.
Anal Chem. 2023 Feb 14;95(6):3238-3246. doi: 10.1021/acs.analchem.2c04084. Epub 2023 Jan 30.
Microglial dysfunction has been identified as a key factor in the pathology of several traumatic and neurodegenerative diseases in the central nervous system. Due to the importance of microglia in various pathological processes, the development of molecular tools to target microglia may be of significance for the clinical diagnosis and treatment of these disorders. In this study, a DNA aptamer, ZH-1c, that binds microglia with high affinity was developed by cell-SELEX and truncated strategies. ZH-1c exhibits promising binding ability under physiological temperatures, high serum stability after being modified, and can be internalized by microglia. Also, the binding target of ZH-1c on microglia was identified as the transmembrane protein CD64, which increased in response to inflammatory stimulation via lipopolysaccharide and interferon-gamma, thus enhancing the affinity of ZH-1c for activated microglia. Based on the above experiments, the DNA aptamer ZH-1c exhibits great potential for the targeting of activated inflammatory microglia and may be suitable as a novel and effective molecular tool for diagnosis and microglia-targeted therapies.
小胶质细胞功能障碍已被确定为中枢神经系统几种创伤性和神经退行性疾病病理学的关键因素。由于小胶质细胞在各种病理过程中的重要性，开发针对小胶质细胞的分子工具对于这些疾病的临床诊断和治疗可能具有重要意义。在这项研究中，通过细胞 SELEX 和截断策略开发了一种与小胶质细胞具有高亲和力结合的 DNA 适体 ZH-1c。ZH-1c 在生理温度下表现出有前途的结合能力，经过修饰后具有高血清稳定性，并可以被小胶质细胞内化。此外，ZH-1c 在小胶质细胞上的结合靶标被鉴定为跨膜蛋白 CD64，其通过脂多糖和干扰素-γ的炎症刺激而增加，从而增强 ZH-1c 与激活的小胶质细胞的亲和力。基于上述实验，DNA 适体 ZH-1c 显示出针对激活的炎症性小胶质细胞的巨大潜力，并且可能适合作为诊断和针对小胶质细胞的治疗的新型有效分子工具。
