We have developed next-generation DNA oligonucleotide aptamers selected from large combinatorial libraries to target a number of proteins. We have developed both in vitro enzymaticcombinatorial selection and split-synthesis chemical combinatorial methods to identify phosphorothioate-modified oligonucleotide �thioaptamers� and next-gen �X�-aptamers to a number of different protein targets for both nanomedicine imaging, therapeutic and diagnostic methods. The X-aptamers also include a large range of chemical (X) modifications to the 5-X-dU position and thus represent a hybrid of aptamer backbone, protein amino acid-like sidechains, and small molecule leads in a self-folding scaffold that can be readily identified by oligonucleotide sequencing. Combinatorial libraries on beads can be readily prepared by click chemistry or amide coupling chemistry to modified-dU sequences. Compared to conventional aptamers, this approach dramatically expands the chemical diversity that can be incorporated to select X-aptamers with high affinity for diverse molecular biomarkers. Large bead-based combinatorial libraries of these aptamers can be rapidly selected. These X-aptamers are being used as antibody substitutes in biomarker identification to tumor cells and tumor vasculature and in various microfluidics and mass spec chips for nanomedicine, proteomics and diagnostics. Examples of application of the bead-based thioaptamer and X-aptamer selection are demonstrated for targeting cancer tissue and cells expressing CD44, E-Selectin and Annexin A2.Disclosure: Financial interest in AM Biotechnologies, Inc.

X-aptamers: A novel small-molecule conjugated aptamer selected from split-pool bead libraries

247th National Meeting (2014)

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