# Development of a novel, RNA-interference-based therapeutic to treat prostate cancer

> **NIH NIH R41** · NUAGO THERAPEUTICS INC · 2024 · $400,000

## Abstract

PROJECT SUMMARY
Prostate cancer (PC) is the most common cancer in men, and the second leading cause of cancer death among
men in the United States. There is a critical unmet need to develop novel, efficacious therapeutics for PC. NUAgo
Therapeutics, Inc. is developing an RNA-interference-based therapeutic for PC based on research conducted at
Northwestern University into a naturally occurring anti-cancer mechanism. This research identified a class of
short (19-22 nt long) double-stranded (ds) interfering RNA molecules (here termed “sRNAs”) that potently target
genes that are essential for cancer cell survival. These sRNAs are derived from CAG trinucleotide repeat (TNR)
sequences that are found in genes associated with several neurodegenerative diseases, including huntingtin
(the cause of Huntington’s disease) and the androgen receptor (AR) gene (the cause of spinobulbar muscular
atrophy [SBMA]/Kennedy disease). Both diseases are associated with reduced cancer incidence. Evidence
indicates that CAG expansions lead to increased production of short interfering RNAs that bind to complementary
transcripts and downregulate their expression. sRNAs containing the CAG repeat (“sCAG”) are extremely toxic
to cancer cells by targeting highly expressed CUG repeat-containing genes, providing both a mechanistic
explanation for the reduced incidence of cancer in patients with certain neurodegenerative diseases and a novel
therapeutic approach for cancer treatment. PC is a particularly attractive target for this novel therapeutic
approach. The number of CAG repeats in the AR gene is inversely correlated with PC incidence, the
aggressiveness of the disease, and the risk of distant metastasis. Longer CAG repeats thus appear to have an
anti-tumor effect, suggesting susceptibility of PC cells to sCAG. The goal of this STTR project is to develop an
sCAG-based therapeutic, which will be delivered to cells using lipopolyplex (LPP) nanoparticles, to treat PC. In
Aim 1, the uptake and activity of sCAG-LPP (“NU002”) will be evaluated in mouse models of prostate cancer,
quantifying both sCAG delivery and silencing activity in PC cells in vivo. Uptake and activity of the NU002 and a
non-toxic control sRNA will be evaluated in both tumor and normal cells in four mouse models, including two
xenograft models of PC and a syngeneic PC model. Uptake will be monitored by fluorescently labeling the
sRNAs, while silencing activity will be measured using a fluorescent reporter gene that includes a corresponding
target sequence. RNA sequencing will be used to measure the expression of target genes in tumors. In Aim 2,
the anti-tumor effects of NU002 will be characterized in vivo in the same four xenograft and syngeneic models
as in Aim 1, measuring the effect on excised tumor size at 4-6 weeks post-treatment. Histological and liver
enzyme analyses will be used to examine toxicity in normal tissues, and RNA sequencing will again be performed
on tumor and normal tissue samples to quantif...

## Key facts

- **NIH application ID:** 11004868
- **Project number:** 1R41CA287846-01A1
- **Recipient organization:** NUAGO THERAPEUTICS INC
- **Principal Investigator:** Marcus E. Peter
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $400,000
- **Award type:** 1
- **Project period:** 2024-09-19 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11004868

## Citation

> US National Institutes of Health, RePORTER application 11004868, Development of a novel, RNA-interference-based therapeutic to treat prostate cancer (1R41CA287846-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/11004868. Licensed CC0.

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