# A biophysical assay for RNA based resistance

> **NIH NIH R43** · NUBAD, LLC · 2020 · $288,889

## Abstract

PROJECT SUMMARY
The world is rapidly heading towards a pre-1940's scenario when it comes to fighting infectious
disease. Antimicrobial resistance is a growing problem on a global scale, greatly hampering our
abilities to quell worldwide epidemics such as tuberculosis and malaria, as well as the simple
staphylococcus infection. The proposed project is significant because unless innovative
strategies are developed to produce robust and effective new classes of antibiotics,
health care costs will continue to climb and we will completely lose our ability to combat
even the most common infection. Current antibiotic treatments originated predominantly from
natural products produced by fungi and bacteria that were able to inhibit the growth of other
organisms, usually by inhibiting cell wall synthesis or maintenance or by inhibiting protein
synthesis. Since penicillin was first isolated by Fleming in 1929, most of the subsequent
generations of antibiotics remain very similar to the original natural products, with functional
groups modified to increase their activity across a broader range of pathogens and decrease
their side effect profiles. Oxazolidones, glycopeptides, b-lactams, and quinolones show some
promise for the future, but gram-negative bacterial infections still remain problematic.
Nucleic acids are promising avenues for drug design, both as therapeutics and as targets. Here
we propose an innovative plan for identification of a novel class of ligands that are
specific for an RNA element that is an important factor in the antibiotic resistance in
dozens of pathogenic bacterial strains, and we propose a biophysical screening assay
for identifying such ligands. First, as outlined in Specific Aim 1, we will characterize a model
nucleic acid domain that has been synthesized commercially with modifications allowing
structural and dynamic properties of this molecule in bulk solution. We will then synthesize
sequence-specific RNA binding ligands and screen these targeted library of conjugates for
sequence-specifically binding and inhibiting the target nucleic acid to (Specific Aim 2). A
successful application of the approach will allow us to silence the resistance pathway for a class
of widely used antibiotics-the aminoglycosides.

## Key facts

- **NIH application ID:** 10080557
- **Project number:** 1R43AI155102-01
- **Recipient organization:** NUBAD, LLC
- **Principal Investigator:** sandra Paige story
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $288,889
- **Award type:** 1
- **Project period:** 2020-07-21 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10080557

## Citation

> US National Institutes of Health, RePORTER application 10080557, A biophysical assay for RNA based resistance (1R43AI155102-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10080557. Licensed CC0.

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