Multi-Target NaV Antisense Compositions for Non-Opioid Pain Relief

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Solution Overview

Problem

Current pain treatment methods, such as opioids and NSAIDs, are associated with significant limitations including addiction, adverse effects, and reduced efficacy over time, while alternative approaches like oligonucleotides targeting sodium channels have not been effectively developed for widespread use.

Innovation Solution

Development of oligonucleotides that bind specifically to the mRNA of sodium channel proteins NaV1.7, NaV1.8, and NaV1.9, preventing their synthesis and reducing pain sensation by downregulating these channels, thereby providing long-term pain relief without the need for opioids.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If opioids are used to treat pain, then pain relief efficacy is improved, but addiction and abuse risks worsen

Engineering Contradiction:

Improvepain relief efficacyVSAvoidaddiction and abuse risks

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces oligonucleotides as an intermediary substance that mediates pain relief by targeting and degrading sodium channel mRNA in nociceptors. This intermediary mechanism provides analgesic effects without activating opioid receptors, thereby eliminating addiction and abuse risks while maintaining pain relief efficacy

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the biochemical mechanism of opioids (which act on neural receptors and carry addiction risk) with a molecular biology-based mechanism (oligonucleotide-mediated mRNA degradation). This substitution changes the fundamental mode of action from receptor-based pharmacology to gene expression modulation, achieving pain relief without harmful side effects

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Ease of operation

If NSAIDs are used to treat pain, then ease of use is improved, but efficacy for severe pain worsens

Engineering Contradiction:

Improveease of useVSAvoidpain relief efficacy

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent changes the therapeutic parameter from simple anti-inflammatory action (NSAIDs) to targeted gene expression suppression (oligonucleotides). By specifically degrading sodium channel mRNA in pain-sensing neurons, the treatment achieves superior efficacy for severe pain while maintaining ease of administration through injectable formulations

Inventive Principle:

Principle #35Parameter changes

3Duration of action of stationary object

If opioids are used long-term, then pain relief duration is improved, but tolerance development worsens

Engineering Contradiction:

Improvepain relief durationVSAvoidefficacy due to tolerance

Core Design Contradiction:

Duration of action of stationary objectVSReliability

Solution Approach 1:

The patent applies preliminary action by degrading sodium channel mRNA before pain signals can be transmitted. This prevents the formation of pain pathways at their origin in nociceptors, providing long-lasting relief without the tolerance development seen with opioids that act on downstream receptors

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent substitutes the opioid mechanism (which suffers from tolerance due to receptor adaptation) with an oligonucleotide mechanism that degrades mRNA templates for sodium channels. This fundamental mechanism change eliminates tolerance development while maintaining long-term pain relief efficacy

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The oligonucleotides effectively decrease pain sensitivity by depleting sodium channels in nociceptor neurons, offering a non-addictive and potentially lower opioid-use treatment option for chronic pain conditions.

Implementation Method 1

When the antisense oligonucleotide (ASO) hybridizes to its target RNA, they form a double-stranded ASO: RNA duplex

Methodology Applied

Scientific EffectHybridization:

Implementation Method 2

recruits an enzyme (RNase H) that degrades a portion of the double-stranded duplex. Degrading the ASO:RNA duplex depletes the neuron of NaV channel mRNA

Methodology Applied

Scientific EffectEnzyme degradation: Enzyme

Implementation Method 3

hybridizes to a pre-mRNA or mRNA encoding a sodium channel protein along a segment of that RNA that is at least about 75% complementary to one of SEQ ID NOs: 1-164 and 166-400 to thereby prevent translation of the RNA into the sodium channel protein

Methodology Applied

Scientific EffectTranslation inhibition:

Data Source

PatentUS20250277222A1Therapeutic compositions for treating pain via multiple targets

Publication Date: 2025.09.04 SUMMIT BIOLABS INC

AI summary

The invention provides non-opioid pain therapeutic compositions that include an antisense oligonucleotide (ASO) complementary to an identified target on a NaV channel mRNA. The ASO hybridizes to its target RNA and forms a duplex that recruits RNase H to degrade the RNA, thereby downregulating NaV channel synthesis, which inhibits the neuron's ability to contribute to the perception of pain. The ASO targets one of the specific identified targets, and may be provided as a gapmer that includes a central DNA segment flanked by modified RNA wings. When the composition is delivered to dorsal root ganglion (DRG) neurons in vitro, the DRG neurons exhibit a dose-dependent knockdown of NaV1.7, NaV1.8, or NaV1.9.