Aptameric Modulation of Relaxivity in MRI Contrast Agents

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DESCRIPTION (provided by applicant): The goal of this project is to develop the next generation of highly-sensitive, targeted, and bio- responsive aptameric modulators of MRI contrast agents. These new reagents would provide in vivo additional structural and functional information, not otherwise available through other imaging modalities. Over the next two years we will provide initial characterization of three different types of interactions between metal ion complexes (e.g., Gd3+DOTA) and their oligonucleotide-based receptors (aptamers), through the following three aims: yIn Aim 1 we will study changes in relaxivity that occur when small molecules attached to gadolinium contrast agents interact with aptamers binding to those molecules. yIn Aim 2 we will first isolate oligonucleotide receptors binding to MRI contrast agents, and then study the impact of aptamer binding on relaxivity. yIn Aim 3 we will isolate aptamers against scaffolds carrying multiple contrast agents. In a follow- up study we will characterize the ability of these aptamers to enhance relaxivity by several possible mechanisms. At the end of this project we will provide preliminary results for several approaches to modify the relaxivity of MRI contrast agents. The approaches based on aptamers are flexible; individual aptamers can be readily engineered into oligomeric and highly-organized structures, and can be made sensitive to other recognition processes. Thus, the main significance of this project is that we will open completely new venues for receptor and metabolic imaging. PUBLIC HEALTH RELEVANCE: Our goal is to provide highly-sensitive, targeted, and bio-responsive oligonucleotide-based (aptameric) modulators of MRI contrast agents. In the context of metabolic and receptor imaging these modulators will provide structural and functional information not available with current imaging modalities. We will focus on demonstrating three different types of interactions through which aptameric modulators are predicted to enhance the relaxivity of MRI contrast agents. An important advantage of our approach based on aptamers is in its flexibility; for example, individual receptors can be readily engineered into oligomeric and highly-organized structures using principles of DNA nanotechnology, and can be made sensitive to other recognition processes.