Complementary Nucleic Acid Nanoparticles for siRNA Delivery

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Solution Overview

Problem

Current RNA interference (RNAi) technologies face challenges in delivering short interfering RNAs (siRNAs) specifically to tumor cells, including transportation, targeting, and stabilization, with existing nanoparticles often requiring complex designs and multiple components for activation.

Innovation Solution

Development of interdependent complementary nucleic acid nanoparticles that activate multiple functionalities upon interaction, forming double-stranded duplexes without the need for toeholds, using reverse complements of existing scaffolds to create 'anti-scaffolds' that simultaneously activate latent functionalities such as transcriptional activation, gene silencing, and optical responses with only two complementary particles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If complex nanoparticle designs with multiple components are used for RNAi delivery, then delivery efficiency and stability are improved, but device complexity increases

Engineering Contradiction:

Improvedelivery efficiencyVSAvoidnanoparticle structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The nanoparticle is segmented into two complementary components (first and second nanoparticles) that self-assemble through sequence complementarity. Each component contains partial functionalities that are activated upon assembly, reducing the complexity of individual components while maintaining overall functionality through modular design

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The nanoparticle components are pre-designed with latent functionalities embedded in their sequences before delivery. These functionalities remain dormant until the nanoparticles interact with target cells and undergo shape switching, at which point the pre-positioned sequences are activated to perform therapeutic functions

Inventive Principle:

Principle #10Preliminary action

2Productivity

If multiple functionalities are activated upon nanoparticle interaction, then therapeutic efficacy is improved, but manufacturing precision requirements increase

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidsequence complementarity

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

The nanoparticle components utilize their own sequence complementarity to drive self-assembly and activation. The first and second nanoparticles automatically recognize and bind to each other through complementary sequences, eliminating the need for external assembly machinery or complex manufacturing processes to ensure precise positioning of functionalities

Inventive Principle:

Principle #25Self-service

3Productivity

If shape switching from compact to extended conformation occurs, then functionality activation is improved, but stability of nanoparticle structure worsens

Engineering Contradiction:

Improvefunctionality activationVSAvoidnanoparticle structure

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The nanoparticle is designed with dynamic conformational flexibility, allowing it to switch between compact stable states (for circulation and delivery) and extended active states (for functionality activation). The sequence complementarity and structural design enable reversible shape switching in response to cellular uptake or environmental cues, balancing stability and functionality

Inventive Principle:

Principle #15Dynamics

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

This approach enables simple, efficient activation of multiple therapeutic and diagnostic functionalities within nanoparticles, improving delivery and stability of siRNAs, reducing immunogenicity, and enhancing therapeutic efficacy while minimizing immune response.

Implementation Method 1

The complementary nanoparticles interact leading to thermodynamically driven conformational changes and to the simultaneous disassembly of the two complementary nanoparticles with re-association of the cognate oligonucleotides to form multiple duplexes

Methodology Applied

Scientific EffectBase pairing: Chemical Bonding

Implementation Method 2

the complementary nanoparticles interact leading to thermodynamically driven conformational changes and to the simultaneous disassembly of the two complementary nanoparticles

Methodology Applied

Scientific EffectThermodynamic driving:

Data Source

PatentUS11512313B2Functionally-interdependent shape switching nucleic acid nanoparticles

Publication Date: 2022.11.29 THE UNIV OF NORTH CAROLINA AT CHAPEL HILL

AI summary

The description provides a molecular switch comprising at least two nanoparticles, wherein a first nanoparticle comprises DNA and/or RNA oligonucleotides, and a second nanoparticle which is complementary to the first nanoparticle comprises reverse complementary DNA and/or RNA oligonucleotides of the first nanoparticle; wherein the complementary nanoparticles interact under physiological conditions leading to thermodynamically driven conformational changes in the first and second nanoparticles leading to their re-association to release one or more duplexes comprising said DNA and/or RNA oligonucleotides and the reverse complementary DNA and/or RNA oligonucleotides, and wherein the nanoparticles are not rings and have no single stranded toeholds.