Hybrid htiRNA/Nanoparticle Complex Stability in Physiological Media

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Solution Overview

Problem

Existing siRNA vehicles face instability in physiological conditions, leading to separation of siRNA and nanoparticles, which hampers their delivery and therapeutic efficacy, particularly in the digestive system.

Innovation Solution

A hybrid DNA/RNA molecule (htiRNA) is developed, comprising two antisense RNA strands and two DNA strands with specific sequence identities and spacer arms, forming a more stable complex with nanoparticles, enhancing stability in physiological media while maintaining RNA interference capability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If siRNA is associated with cationic lipid nanoparticle via electrostatic interaction, then intracellular bioavailability is improved, but stability in physiological medium deteriorates

Engineering Contradiction:

Improveintracellular bioavailabilityVSAvoidstability in physiological medium

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent uses a composite nanoparticle structure combining cationic lipids with protective coatings (such as PEG-lipids or cholesterol) to create a dual-function vehicle that maintains both electrostatic binding capability and physiological stability. This composite approach allows the nanoparticle to retain positive charge for siRNA binding while the outer coating provides steric stabilization against physiological conditions.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent modifies the physical and chemical parameters of the nanoparticle, including adjusting the lipid composition ratio, controlling particle size distribution, and optimizing surface charge density. These parameter changes enable the nanoparticle to maintain appropriate electrostatic interaction with siRNA while reducing premature dissociation in physiological media through controlled stability characteristics.

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If siRNA vehicle is designed for oral administration, then route versatility is improved, but stability in intestinal media deteriorates

Engineering Contradiction:

Improveoral administration capabilityVSAvoidstability in intestinal media

Core Design Contradiction:

Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

The patent introduces protective intermediary layers such as PEGylated lipids or biocompatible polymers that act as mediators between the siRNA-nanoparticle complex and the harsh intestinal environment. These intermediary coatings protect the complex from enzymatic degradation and pH extremes while allowing the nanoparticle to reach its target intact.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The nanoparticle is pre-coated with protective materials and optimized in advance to withstand the challenging intestinal conditions before encountering them. The formulation includes stabilizers and protective lipids that are incorporated beforehand to cushion against the harsh environment of intestinal media, including enzymes and varying pH levels.

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

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 htiRNA/nanoparticle complex achieves enhanced stability and efficient delivery of siRNA across physiological barriers, ensuring effective modulation of gene expression.

Implementation Method 1

the attaching of a siRNA which is an anionic molecule (net negative charge) is possible on a cationic lipid nanoparticle (net positive charge) via electrostatic interaction

Methodology Applied

Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

the nucleotide sequence SC1 is hybridized via complementarity to a first of the two antisense RNA strands

Methodology Applied

Scientific EffectHybridization via complementarity: Chemical Bonding

Data Source

PatentUS12441999B2Hybrid htiRNA/nanoparticle complex and use thereof for treating a disease of the digestive system

Publication Date: 2025.10.14 COMMISSARIAT A LENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES

AI summary

A hybrid DNA/RNA molecule, or a complex thereof with at least one nanoparticle, may be used for the prevention or treatment of a disease, in particular a disease of the digestive system.