Peptide-based CE-SELEX enables convenient isolation of aptamers specifically recognizing CD20-expressing cells

• Published in: Bioorganic & medicinal chemistry 2024-08, Vol.110, p.117831, Article 117831
• Main Authors: Cossu, Jordan, Ravelet, Corinne, Martel-Frachet, Véronique, Peyrin, Eric, Boturyn, Didier
• Format: Article
• Language: English
• Subjects: Antigens, CD20 - chemistry; Antigens, CD20 - metabolism; Aptamer; Aptamers, Nucleotide - chemistry; Capillary electrophoresis; CD20; Cell Line, Tumor; Chemical Sciences; Electrophoresis, Capillary; Humans; Peptides - chemistry; Peptides - isolation & purification; Peptides - metabolism; Peptides - pharmacology; SELEX; SELEX Aptamer Technique
• ISSN: 0968-0896; 1464-3391; 1464-3391
• DOI: 10.1016/j.bmc.2024.117831

The CE-SELEX was used for the selection of DNA aptamers that recognize the CD20 antigen, which is a key target for several diseases including lymphoma and autoimmune diseases. Two aptamers were shown to specifically recognize a relevant CD20-expressing human Raji cell line with Kd found in the micromolar range. [Display omitted] •New anti-CD20 aptamers were selected by using peptide-based CE-SELEX method.•Aptamer 1 specifically binds a CD20-expressing Raji human cell line.•The CE-SELEX is a suitable alternative method to the conventional Cell-SELEX avoiding a delicate biological procedure. 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 Kd 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.