New Methods to Generate High-Performance Aptamers for in Vivo Monitoring of Small Molecules
NIBIB - National Institute of Biomedical Imaging and Bioengineering
About This Grant
Summary. Aptamers – a versatile class of synthetic, nucleic-acid-based receptors – offer unique advantages for molecular sensing. Because of the hydrophilicity of oligonucleotides, for example, aptamers offer a key advantage relative to antibodies in terms of remaining soluble even when partially or fully unfolded. This distinctive characteristic renders it straightforward to engineer aptamers that fold and unfold in response to target binding and dissociation. In turn, this coupling of molecular recognition to a large-scale conformational change enables the construction of biosensors supporting real-time in vivo molecular measurements and chemo- responsive, materials whose properties change in response to a specific molecular cue. A major disadvantage of aptamers, however, is that their affinity and specificity are often insufficient for use under physiological conditions. Here, we present strong evidence that this poor performance is not an intrinsic limitation of nucleic acids, but instead arises from the limitations of conventional aptamer selection techniques. Building on this, we describe advanced aptamer selection and maturation approaches that we believe will surmount these limitations. In Aim 1, we propose the development of a powerful new aptamer selection approach, nuclease-assisted systematic evolution of ligands by exponential enrichment (NA-SELEX), which eliminates the need to attach either the target or the library to a solid support. This provides many important advantages over existing selection approaches, including the ability to simultaneously apply both thermodynamic and kinetic stringency and to easily carry out aptamer selection under physiologically relevant conditions, leading to enhanced in vivo aptamer performance. In Aim 2, we will complement NA-SELEX by developing an innovative “aptamer maturation” approach, Motif-SELEX, that can greatly improve the performance of underperforming first-generation aptamers. Motif-SELEX does this by providing new opportunities to explore the deep sequence space for a given aptamer during the selection process in order to optimize the geometry and complexity of that aptamer’s ligand-binding site, thereby increasing both its affinity and specificity. Finally, in Aim 3, we will showcase the improved performance and utility of the resulting aptamers by converting them into real-time biosensors to enable the currently unachievable feat of measuring a chemically diverse set of biomedically-important, low-concentration small-molecule targets in vivo. In the short term, the successful conclusion of our research program will yield sensors that enable clinically and scientifically useful real-time in vivo measurement of numerous biomedically- important low-molecular-weight analytes. The more far-reaching impact of this work will be the development of methods supporting the selection of aptamers with unprecedentedly high performance, greatly expanding the utility of these reagents for a wide range of biomedical applications.
Grant Summary
New Methods to Generate High-Performance Aptamers for in Vivo Monitoring of Small Molecules is a NIBIB - National Institute of Biomedical Imaging and Bioengineering grant providing up to $691K for university, nonprofit, healthcare org. Applications are due 2030-02-28 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $691K
2030-02-28
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New Methods to Generate High-Performance Aptamers for in Vivo Monitoring of Small Molecules: Frequently Asked Questions
Who is eligible for the New Methods to Generate High-Performance Aptamers for in Vivo Monitoring of Small Molecules?
New Methods to Generate High-Performance Aptamers for in Vivo Monitoring of Small Molecules is offered by NIBIB - National Institute of Biomedical Imaging and Bioengineering and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the New Methods to Generate High-Performance Aptamers for in Vivo Monitoring of Small Molecules provide?
New Methods to Generate High-Performance Aptamers for in Vivo Monitoring of Small Molecules provides up to $691K per award from NIBIB - National Institute of Biomedical Imaging and Bioengineering. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the New Methods to Generate High-Performance Aptamers for in Vivo Monitoring of Small Molecules deadline?
Applications for New Methods to Generate High-Performance Aptamers for in Vivo Monitoring of Small Molecules are due 2030-02-28 (open). Because deadlines can change, verify the date with the funder, NIBIB - National Institute of Biomedical Imaging and Bioengineering, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the New Methods to Generate High-Performance Aptamers for in Vivo Monitoring of Small Molecules?
To apply for New Methods to Generate High-Performance Aptamers for in Vivo Monitoring of Small Molecules, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIBIB - National Institute of Biomedical Imaging and Bioengineering.