Duke University
Grant: $258,960 - National Institutes of Health - May. 21, 2009
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Award Description: RNA aptamers have been generated against a variety of proteins including a few cell surface receptors. In general such aptamer act as potent inhibitors of their target proteins both in vitro and in vivo. Moreover, a few of these antagonistic aptamers have been evaluated in clinical trials including one we developed against factor IXa and one that has been approved by the FDA for treating age related macular degeneration. However to date, no aptamer has been described that can act as an agonist. In this proposal we explore the ability of aptamers to activate cell surface receptors. In the preliminary results section we describe a series of unpublished studies demonstrating that dimeric versions of aptamers that we have made against two different receptors on T-cells, 4-1BB and OX40, are able to activate these receptors on primary murine T-cells resulting in T-cell proliferation, cytokine release and enhanced antitumor vaccine activity in murine tumor immunotherapy models. To our knowledge these are the first two aptamers that have been identified that can act as agonists. Here we are seeking support to evaluate the activity of these two agonistic aptamers as well as determine whether a third aptamer that we have recently made against stem cell factor receptor, c-Kit, can also act as an agonist and activate stem cell factor receptor and erythropoiesis. Analysis of these aptamers will include assessing their ability to deliver siRNAs to primary T-cells and T-cell lymphoma and leukemia cell lines (OX40 and 4-1BB aptamers) and erythrocyte precursors and c-Kit positive tumor cells (cKit aptamer). Technologies that mediate targeted delivery of small interfering RNAs (siRNAs) are needed to improve the therapeutic efficacy, safety and cost effectiveness of siRNA-based therapeutic agents.
Project Description: See Award Description
Jobs Summary: Jobs created and retained in the following fields: FACULTY RESEARCH & SCHOLARSHIP SCIENTIFIC/ELEC/RES TECHNOLOGY (Total jobs reported: 1)
Project Status: Less Than 50% Completed
This award's data was last updated on May. 21, 2009. Help expand these official descriptions using the wiki below.
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