{Reference Type}: Journal Article
{Title}: A Bispecific Chimeric Aptamer Design Platform Based on c-MET Aptamer with a Replaceable Redundant Region.
{Author}: Zhang X;Zhang N;Sun H;Li D;Long Z;Sheng J;Zu S;Bing T;Shangguan D;
{Journal}: Chembiochem
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jun 24
{Factor}: 3.461
{DOI}: 10.1002/cbic.202400501
{Abstract}: Molecular engineering enables the creation of aptamers with novel functions, but the prerequisite is a deep understanding of their structure and recognition mechanism. The cellular-mesenchymal epithelial transition factor (c-MET) is garnering significant attention due to the critical role of the c-MET/HGF signaling pathway in tumor development and invasion. This study reports a strategy for constructing novel chimeric aptamers that bind to both c-MET and other specific proteins. c-MET was identified to be the molecular target of a DNA aptamer, HF3-58, selected through cell-SELEX. The binding structure and mechanism of HF3-58 with c-MET were systematically studied, revealing the scaffold, recognition, and redundancy regions. Through molecular engineering design, the redundancy region was replaced with other aptamers possessing stem-loop structures, yielding novel chimeric aptamers with bispecificity for binding to c-MET and specific proteins. A chimeric bispecific aptamer HF-3b showed the ability to mediate the adhesion of T-cells to tumor cells, suggesting the prospective utility in tumor immunotherapy. These findings suggest that aptamer HF3-58 can serve as a molecular engineering platform for the development of diverse multifunctional ligands targeting c-MET. Moreover, comprehensive understanding of the binding mechanisms of aptamers will provide guidance for the design of functional aptamers, significantly expanding their potential applications.