Research Project
8312302
DESCRIPTION (provided by applicant): Aptamers are nucleic acid based affinity reagents that can be selected in vitro from large combinatorial libraries. As an affinity reagent they have inherent advantages as they are chemically synthesized, thermostable, immunologically neutral, significantly cheaper than antibody reagents and can be evolved for both specificity and affinity. Conversely, the process to generate useful aptamer reagents is lengthy, requiring significant experience and time to generate a useful reagent; frequently months for 8-15 rounds of library selection. Therefore, despite the promise of aptamer technology and the notable success of aptamer therapeutics in the short time the technology has been available, the threshold for entry into this field is inhibited by this labor-intensive process and mixed success. Phase I feasibility studies showed that DNA aptamers with low nanomolar dissociation constants (Kd < 3 nM) can be generated in just 3 rounds of selection, since extended to 5 proteins. This work has clearly shown the feasibility of our technology. From this foundation, this application will help fund commercialization of this aptamer selection platform, the reagents and protocol. We expect that successful commercialization will have a major impact on the advancement of diagnostics, therapeutics, and the emerging proteomics applications where reagent demands far outstrip supply. Provide key words (8 maximum) to identify the research or technology. aptamer, Pro-SELEX, affinity, selection, Provide a brief summary of the potential commercial applications of the research. The Pro-SELEX platform and sequencing protocol 60-80% both the workload and chance of failure for selection of aptamer affinity reagents. This generates a significantly more appealing approach to aptamer selection likely to expand the application of this technology into proteomics and diagnistic reagents. PUBLIC HEALTH RELEVANCE: Aptamers are molecular recognition molecules analogous to monoclonal antibodies except that they are made in test tubes using nucleic acid libraries. They have demonstrated enormous diversity and potential since they were first used 20 years ago, but they are very time consuming and troublesome to develop. This project describes a platform that standardizes and automates generation of aptamer reagents. It has to potential to significantly accelerate the development of aptamer tools for use in drug delivery, therapeutics as well as basic research and diagnostic sciences.
