Aptamers have been largely unable to traverse the translational divide between lab bench and clinic despite their numerous applications in diagnostics and as molecular probes in biochemical and biomedical research. Currently, FDA-approved Macugen (Pegatinib) stands as the sole example of an aptamer drug. This study aims to address several translational obstacles by demonstrating the facile transcription of a 2'-fully modified (fm) RNA library by a novel T7 RNA polymerase mutant, the direct selection of aptamers from a fmRNA library that bind Staphylococcus aureus Protein A (SpA), and the superior nuclease and serum stability of these aptamers compared to 2'-partially modified RNA variants. Characterizations of fmRNA aptamers binding to purified SpA and to endogenous SpA present on the surface of S. aureus cells demonstrate fmRNA aptamer selectivity, stability, and unexpected hydrophobicity. fmRNA aptamers were able to functionalize, stabilize, and deliver aggregation-prone silver nanoparticles (AgNPs) to S. aureus with SpA-dependent antimicrobial effects. This study describes a novel aptamer class with considerable potential to address unmet needs for the translational application of nucleic acid-based affinity molecules.

Selection of highly stable aptamers from a 2'-fully modified RNA library

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.