ZnO Nanoparticles Stabilize mRNA Against Thermal Degradation

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Solution Overview

Problem

Current RNA-based therapeutics, such as COVID-19 mRNA vaccines, face challenges with temperature stability, requiring cold chain storage to maintain activity, which limits their widespread deployment and efficacy.

Innovation Solution

Zinc oxide nanoparticles (ZnO NPs) are used to stabilize RNA by enhancing its temperature stability through interaction, forming complexes that retain structural and functional integrity even at elevated temperatures, and are administered via various routes to ensure effective delivery and immune response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If RNA-based therapeutics are stored at higher temperatures, then storage and distribution become easier, but RNA stability and activity are compromised

Engineering Contradiction:

Improvestorage and distribution convenienceVSAvoidRNA stability

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

Zinc oxide nanoparticles serve as an intermediary substance that mediates between RNA and the environmental temperature. The nanoparticles bind to RNA through electrostatic interactions, forming a protective complex that shields RNA from thermal degradation and nuclease attack, enabling stable storage at higher temperatures without cold chain requirements

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention creates a composite material system consisting of zinc oxide nanoparticles combined with RNA. This composite structure leverages the stabilizing properties of zinc oxide (which has been shown to stabilize protein and nucleic acids) to protect RNA, resulting in a material that maintains RNA integrity at temperatures where free RNA would degrade

Inventive Principle:

Principle #40Composite materials

2Reliability

If cold chain storage is implemented to maintain RNA activity, then RNA stability is preserved, but deployment complexity and cost increase

Engineering Contradiction:

ImproveRNA stabilityVSAvoidcold chain infrastructure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The invention extracts the cold chain requirement from the RNA storage system by introducing zinc oxide nanoparticles. The nanoparticles are administered directly to subjects or stored without refrigeration, and they actively protect RNA in vivo, thereby removing the need for complex cold chain infrastructure while maintaining RNA stability and activity

Inventive Principle:

Principle #2Taking out (Extraction)

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

ZnO NPs significantly increase RNA stability, allowing for storage and maintenance of antigenicity at higher temperatures, supporting the development of stable RNA vaccines and therapeutics that can be deployed without the need for cold chain storage.

Implementation Method 1

RNA interaction to zinc oxide nanoparticle (ZnO NP) increases stability in serum, liver and tumor homogenates protecting against RNase-mediated degradation and potentiates immune response in cell culture and mouse models

Methodology Applied

Scientific EffectNanoparticle interaction:

Implementation Method 2

ZnO NPs significantly increase RNA stability, allowing for storage and maintenance of antigenicity at higher temperatures

Methodology Applied

Scientific EffectEnzyme inhibition:

Data Source

PatentUS20240307552A1RNA stabilizing nanoparticles

Publication Date: 2024.09.19 KANSAS STATE UNIV RES FOUND

AI summary

The present disclosure provides ZnO-based compositions that stabilize mRNA and RNA as well as provide compositions and therapies to treat or prevent cancer and viral as well as microbial diseases.