16 - Fully modified nucleotide aptamer selection against cancer biomarker Igf-1r for theragnostic application
University of Texas at Austin
Cell & Molecular Biology
Aptamers are short oligonucleotides that are designed to bind protein targets with high affinity and specificity. To be successful as a therapeutic agent, aptamers must satisfy all of the following requirements: high affinity and specificity, economic synthesis, tolerability, and stability. The last of these requirements is central to this study as €natural€ DNA and RNA aptamers are susceptible to nuclease degradation leading to minimal in vivo exposure. However, it has been shown that modifications at the 2€-position of ribose (and deoxyribose) can greatly increase resistance to the nuclease-mediated degradation compared with their natural counterpart. The second requirement, high affinity and specificity, can be sacrificed if such modifications are applied post-selection. It is for that reason that 13 different (12 novel) mutant T7 RNA polymerases have been tested for the ability to efficiently synthesize modified sequences and libraries. Of the tested compositions, most notable is fGmH (2€F guanidine, 2€O-Methyl adenosine, cytosine, and uracil triphosphates). The aim of this project, therefore, is to isolate an aptamer that binds tightly and specifically to cancer biomarker Igf-1r. Such an aptamer is intended for use as a targeting agent with both therapeutic and diagnostic application (theragnostic).