# Role of noncoding RNA in alcohol action

> **NIH NIH U01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $454,348

## Abstract

Project Summary
Ethanol-induced changes in the brain transcriptome underlie the development and persistence of 
alcohol use disorder (AUD). INIA-N investigators and others have discovered that ethanol induces 
specific and dramatic alterations in a highly restricted group of noncoding RNAs (ncRNAs) that 
includes long ncRNAs (lncRNAs).  We posit that these ethanol responsive lncRNAs coordinate AUD 
brain transcriptomes.  Specific Aim 1 will test the hypothesis that individual lncRNAs are key 
regulators of ethanol drinking.  To test this hypothesis, genetically engineered mice with altered 
expression of lncRNAs will be created and analyzed.  Those mutant lines with altered drinking 
behavior will be scrutinized for mechanistic insight by multiple INIA-N investigators.
A barrier to the study of ncRNA function in brain is the dearth of efficient methods of 
noninvasively delivering ncRNAs and/or ncRNA antagonists to large portions of the brain. Here we 
posit that intransally administered exosomes (endogenously produced, liposome like nanoparticles) 
can be harnessed to deliver ncRNA anatagonists or mimics throughout the brain. This approach can 
also be used to deliver drugs preferentially to brain.  Such an approach would target drugs 
selectively to the desired site of action (brain) while avoiding peripheral toxicities that limit 
therapeutic efficacy. Because this approach has the dual benefits of target specificity and 
noninvasiveness, it has tremendous translational potential.  Specific Aim 2 will test the 
hypothesis that exosomes can be harnessed as effective ncRNA/drug delivery vehicles to modulate 
ethanol drinking.
Genetically engineered rodents permit investigation of the involvement of putative ethanol targets 
in the context of whole animal behavioral responses.  Because hypotheses concerning putative 
ethanol targets must ultimately explain ethanol-induced behavioral phenotypes, whole-animal 
experiments represent the most rigorous test of relevance.  To this end, Specific Aim 3 will create 
designer mice for both INIA-N and INIA-Stress investigators. Genetically engineered animals will be 
produced using state of the art CRISPR/Cas9 gene editing technology.  This collaborative Specific 
Aim is the continuation of the INIA-West Genetically Engineered Rodents Core that was funded during 
the previous project period.

## Key facts

- **NIH application ID:** 10086355
- **Project number:** 5U01AA020889-10
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Gregg E. Homanics
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $454,348
- **Award type:** 5
- **Project period:** 2011-09-05 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086355

## Citation

> US National Institutes of Health, RePORTER application 10086355, Role of noncoding RNA in alcohol action (5U01AA020889-10). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10086355. Licensed CC0.

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