dsRNA Cationic Polymer Quenching Agent Soil Binding

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Solution Overview

Problem

The stability and bioavailability of double-stranded RNA (dsRNA) are compromised in harsh environmental conditions, leading to rapid degradation and reduced efficacy in silencing gene expression in target organisms, particularly in soil where it is used for pest control, due to binding with cationic polymers and charged particles.

Innovation Solution

A method involving a composition of a cationic polymer and dsRNA, where a quenching agent neutralizes positive charges on the complex, preventing binding with negatively charged molecules in soil, thereby enhancing stability and mobility of the dsRNA for effective post-transcriptional silencing of target genes in subterranean plant pests.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If dsRNA is stabilised by encapsulating or binding it to a cationic polymer, then stability and duration of action are improved, but the complex binds to negatively charged particles in soil which reduces availability and impedes movement to target organisms

Engineering Contradiction:
Improvestability of dsRNAVSAvoidbinding to negatively charged particles
Core Design Contradiction:
Stability of the object's compositionVSObject-generated harmful factors

Solution Approach 1:

The patent modifies the charge parameter of the polymer complex by introducing a quenching agent that neutralizes positive charges on the cationic polymer. This parameter change transforms the complex from positively charged (which binds to negatively charged soil particles) to neutral or negatively charged, thereby preventing harmful adsorption to soil components while maintaining stability enhancement.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The quenching agent acts as an intermediary substance that mediates between the cationic polymer-dsRNA complex and the soil environment. By introducing this intermediate agent, the patent prevents direct harmful interaction between the positively charged complex and negatively charged soil particles, allowing the complex to maintain stability without suffering from adsorption issues.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If dsRNA is applied directly to target organisms, then bioavailability is maintained, but stability is poor and half-life is less than 12-24 hours in soil

Engineering Contradiction:
Improvebioavailability of dsRNAVSAvoidhalf-life of dsRNA
Core Design Contradiction:
Ease of operationVSDuration of action of stationary object

Solution Approach 1:

The patent creates a composite material system consisting of cationic polymer, dsRNA, and quenching agent. The cationic polymer provides stability and protection against degradation, while the quenching agent modifies the charge characteristics to prevent soil binding. This composite approach combines multiple functional components to simultaneously achieve both stability enhancement and bioavailability maintenance.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent changes the charge parameter of the polymer complex to neutral or negative values, which fundamentally alters the interaction behavior with soil particles. This parameter modification allows the complex to resist adsorption to negatively charged soil surfaces, thereby maintaining mobility and bioavailability while benefiting from the stabilizing effect of polymer encapsulation.

Inventive Principle:
Principle #35Parameter changes

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 approach significantly improves the stability and bioavailability of dsRNA, allowing it to maintain biological activity and effectively silence target genes in subterranean pests, such as corn rootworms, by reducing binding with soil components and enhancing movement and delivery.

Implementation Method 1

a quenching agent capable of substantially neutralising positive charges on the complex... preventing binding with negatively charged molecules present in soil

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Data Source

PatentEP3523431B1Improvements in or relating to gene silencing
Publication Date: 2020.10.28 SYNGENTA PARTICIPATIONS AG
  • EP3523431B1 patent drawingFigure 1
  • EP3523431B1 patent drawingFigure 2
  • EP3523431B1 patent drawingFigure 3

AI summary

The present invention provides for methods of delivering polynucleotides to subterranean plant pests. In particular, the present invention relates to methods of reducing the binding of a composition, comprising polynucleotide and a cationic polymer, to soil by substantially quenching positively charged residues with a quenching agent. The invention also comprises compositions comprising a cationic polymer, a polynucleotide and a quenching agent.