Development of Protein-targeted Aptamers for Cancer Therapeutics

Abstract

Aptamers are single-stranded DNA or RNA molecules capable of recognizing and tightly binding to a variety of targets with high specificity. Treatment of brain and CNS disorders remains the holy grail of drug delivery due to the obstacle imposed by the blood-brain barrier (BBB). Bearing various advantages such as small size, low immunogenicity, and ease of large-scale synthesis at affordable costs, aptamers are an emerging field of novel cancer therapeutics that demonstrate the potential for BBB crossing. Here, we aimed to develop aptamer-based targeting vehicles utilizing the endogenous iron-loading pathway involving the transferrin receptor (TfR, or CD71) and its ligand, transferrin (Tf). We demonstrated our expansive effort in the discovery of Tf binding aptamers via protein-SELEX and the characterization, cross-reactivity, and preliminary data for future applications of a CD71 binding aptamer, tJBA.