Next Generation X-Aptamers for Identification of Personalized Biomarkers in Cancer
Conference Recording Jan 07, 2013
About the SpeakerDavid G. Gorenstein, Ph.D., is Associate Dean for Research and interim Chair of the Department of NanoMedicine and Biomedical Engineering at the University of Texas Health Sciences Center at Houston. He is also Deputy Director of the Institute of Molecular Medicine and James T. Willerson Distinguished Chair and Director, Center for Proteomics and Systems Biology.
We have developed novel, next-generation modified DNA oligonucleotide aptamers selected from large combinatorial libraries to target a number of protein biomarkers. We have developed both in vitro enzymatic combinatorial 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 proteomics and biomarker discovery. 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. 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 and thioaptamers are being used as antibody substitutes in biomarker identification to tumor cells and tumor vasculature and in various microfluidics and mass spec chips for 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 and E-Selectin.