A Branched SELEX Approach Identifies RNA Aptamers That Bind Distinct HIV-1 Capsid Structural Components

• DOI: 10.1021/acsinfecdis.3c00708
• Publication Date: 2024-07-17T12:49:25Z
• Authors: Paige R. Gruenke; Miles D. Mayer; Rachna Aneja; William J. Schulze; Zhenwei Song; Donald H. Burke; Xiao Heng; Margaret J. Lange
• Keywords: Aptamer; Random hexamer; Structural Biology

The HIV-1 capsid protein (CA) assumes distinct structural forms during replication, each presenting unique, solvent-accessible surfaces that facilitate multifaceted functions and host factor interactions. However, functional contributions of individual CA structures remain unclear, as evaluation presents several technical challenges. To address this knowledge gap, we identified CA-targeting aptamers with different specificities, which emerged through a branched SELEX approach using an aptamer library previously selected to bind the hexamer lattice. Subsets were either highly specific for lattice or bound both hexamer. We then evaluated four representatives reveal regions required binding, highlighting interesting features challenges in structure determination. Further, demonstrate binding biologically relevant aptamer-mediated affinity purification from cell lysates without virus modification, supporting development form-specific exciting new tools study CA.