# Development of anti-sense oligonucleotides as a therapeutic for cancer pain through selective block of sodium channel pain targets

> **NIH NIH R44** · QUIVER BIOSCIENCE INC. · 2022 · $995,305

## Abstract

Project Summary: Development of anti-sense oligonucleotides as a therapeutic for cancer pain by
selectively reducing sodium channel expression
Effective treatment of cancer pain is a large unmet medical need, as opioids, the current standard of care lack
efficacy and cause addiction. For end-of-life cancer patients and estrogen receptor- positive breast cancer
patients with long life expectancy, more effective therapeutic approaches for pain are needed. Antisense
oligonucleotides (ASOs) bind to and induce degradation of RNA transcripts with specific sequences, enabling
selective protein knockdown (KD) with long duration of action (weeks or months), to deliver long-term relief.
ASOs can also be used in combination, to reduce the expression of multiple proteins for increased efficacy. As
a modality, ASOs have been successfully applied in the clinic to treat severe neurological disease.
We target the voltage gated sodium channels (Navs) selectively expressed in dorsal root ganglion neurons
(Nav1.7, Nav1.8 and Nav1.9), which are implicated in pain transmission and specifically in cancer pain.
Reduction of channel expression aims to overcome the limitations of small molecule state-dependent channel
blockers, if the channel should be blocked in a state-independent manner for efficacy. Preliminary results with
our designed ASOs show >70% mRNA KD for several Navs in rat dorsal root ganglion sensory neurons (DRGs).
We apply a novel platform to design ASOs for specific knockdown of Nav channels. For pain targets and
indications, QuellTx also has an exclusive worldwide license to breakthrough technology: (i) An in vitro cellular
model for cancer pain (developed through SBIR funding by NCI), where primary DRG neurons are bathed in a
physiologically-relevant mixture of inflammatory mediators secreted by tumors, or ‘cancer-SPARC’. The SPARC-
treated neurons become hyperexcitable, mimicking the cellular pain response. (ii) An all optical electrophysiology
high throughput readout for neuronal excitability (Optopatch), allowing recordings from 100s of individual neurons
in parallel with high temporal resolution. This platform enables us to determine the impact of modulating
expression of Nav1.7, 1.8 and 1.9, alone or in combination, on the pain-in-a-dish phenotype.
In Phase I we propose to leverage our ASO design capabilities, combined with the breakthrough technology to:
(a) identify ASOs for selective modulation of expression of Nav channel pain targets and (b) determine the
combination of ASOs and %mRNA knock down for maximal phenotypic effect in vitro. We will select ASOs that
efficiently knockdown Nav channels and reverse the pain phenotype induced by cancer-SPARC. In Phase II we
will determine the PK/PD (%mRNA KD) in rats, and the % mRNA KD needed for efficacy in a rat model of cancer
pain, while optimizing human cross-reacting with cynmolgous monkey (cyno) ASOs for efficacy in human DRG
neuronal models of pain. Our ultimate goal is to advance optimized ASO...

## Key facts

- **NIH application ID:** 10410515
- **Project number:** 5R44CA247110-03
- **Recipient organization:** QUIVER BIOSCIENCE INC.
- **Principal Investigator:** Owen B. McManus
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $995,305
- **Award type:** 5
- **Project period:** 2020-09-07 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10410515

## Citation

> US National Institutes of Health, RePORTER application 10410515, Development of anti-sense oligonucleotides as a therapeutic for cancer pain through selective block of sodium channel pain targets (5R44CA247110-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10410515. Licensed CC0.

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