University Grenoble Alpes, CNRS, DCM UMR 5250, 38058 Grenoble Cedex 9, France; University Grenoble Alpes, CNRS, DPM UMR 5063, 38041 Grenoble Cedex 9, France.
University Grenoble Alpes, CNRS, DPM UMR 5063, 38041 Grenoble Cedex 9, France.
Bioorg Med Chem. 2024 Aug 1;110:117831. doi: 10.1016/j.bmc.2024.117831. Epub 2024 Jul 6.
The CD20 antigen is a key target for several diseases including lymphoma and autoimmune diseases. For over 20 years, several monoclonal antibodies were developed to treat CD20-related disorders. As many therapeutic proteins, their clinical use is however limited due to their nature with a costly biotechnological procedure and side effects such as the production of anti-drug neutralizing antibodies. Nucleic acid aptamers have some advantages over mAbs and are currently investigated for clinical use. We herein report the selection of DNA aptamer by using a peptide-based CE-SELEX (Capillary Electrophoresis-Systematic Evolution of Ligands by Exponential Enrichment) method. It was demonstrated that these aptamers bind specifically a CD20-expressing human cell line, with K estimated from isothermal titration calorimetry experiments in the micromolar range. This study demonstrates that the CE-SELEX is suitable as alternative method to the conventional Cell-SELEX to discover new cell-targeting compounds.
CD20 抗原是包括淋巴瘤和自身免疫性疾病在内的多种疾病的关键靶点。20 多年来,已经开发了几种单克隆抗体来治疗与 CD20 相关的疾病。与许多治疗性蛋白质一样,由于其昂贵的生物技术工艺和副作用(如产生抗药物中和抗体),其临床应用受到限制。核酸适体相对于 mAbs 具有一些优势,目前正在研究用于临床应用。本文报告了使用基于肽的 CE-SELEX(毛细管电泳-配体指数富集系统进化)方法选择 DNA 适体。结果表明,这些适体特异性结合表达 CD20 的人细胞系,通过等温滴定量热实验估计 Kd 值在微摩尔范围内。这项研究表明,CE-SELEX 适合作为传统 Cell-SELEX 的替代方法,用于发现新的细胞靶向化合物。