# ncRNA: structure, function and inhibition

> **NIH NIH R35** · UNIVERSITY OF WASHINGTON · 2024 · $673,638

## Abstract

Targeting RNA with small molecules with the pharmacological properties of
successful drugs would open-up an untapped universe of pharmaceutical targets
within mRNAs and ncRNAs. However, the successful discovery of potent and cell-active
inhibitors of RNA requires a fundamental understanding of RNA recognition by small
molecules. This knowledge is largely missing, because there are very few examples
(<10) in the academic and patent literature of small molecules that bind to RNA potently
(nM) and specifically and that also possess drug-like chemistry.
 In the first 4 years of this MIRA project, we have discovered a class of drug-
like molecules that bind to several RNAs with nanomolar affinity and specificity.
This breakthrough opens-up an exceptional opportunity to investigate the
fundamental principles of RNA recognition. The very broad impact and significance of
the discovery is validated, in addition to 22 academic publications and 2 patents, by a
spin-off which licensed the use of the chemistry in oncology, vetted by luminaire
medicinal chemists, credited together with the development of 4 blockbuster drugs.
 The premise of this continuation is that a fundamental understanding of the
principles of molecular recognition of RNA by these drug-like small molecules, of
the structural, chemical, energetic and dynamic properties that lead to potent binding and
specificity, would allow us to identify additional privileged scaffolds for RNA, and to
discover potent inhibitors of replication of pathogenic RNA viruses.
 To achieve this goal, we will dissect RNA-small molecule recognition through 3D
structure determination and investigations of the chemistry, thermodynamics and
dynamics of binding. We will also develop the chemistry we have discovered to address
unmet clinical needs in addressing infections by Dengue and Zika viruses, where
vaccination has so far been unsuccessful. We will collaborate with infectious disease
biologists to conduct experiments in cells and model organisms to examine anti-
viral activity in biologically meaningful contexts and demonstrate cellular RNA
engagement.

## Key facts

- **NIH application ID:** 10888136
- **Project number:** 5R35GM126942-07
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Gabriele Varani
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $673,638
- **Award type:** 5
- **Project period:** 2018-04-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10888136

## Citation

> US National Institutes of Health, RePORTER application 10888136, ncRNA: structure, function and inhibition (5R35GM126942-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10888136. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*