Protein-DNA Core-Shell Nanoparticles for Supramolecular Assembly

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Solution Overview

Problem

Current methods for programming the assembly of proteins into supramolecular structures are limited by structural constraints, poor bioavailability, degradation by cellular proteases, and aggregation upon storage, which restricts the catalytic functionalities and therapeutic potential of proteins.

Innovation Solution

The development of protein/DNA core-shell nanoparticles, where a protein core is surrounded by a dense shell of oligonucleotides, allowing for the construction of crystalline materials with controlled lattice parameters and symmetries, and providing stability against degradation and aggregation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If proteins are used as building blocks for supramolecular assemblies, then catalytic functionalities are incorporated, but structural constraints limit the ability to engineer lattices

Engineering Contradiction:

Improvecatalytic functionalitiesVSAvoidlattice engineering complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent introduces DNA oligonucleotides as intermediary building blocks that mediate between protein components and the lattice structure. The DNA shells functionalized with sticky ends serve as programmable intermediaries that enable precise lattice engineering while preserving protein catalytic functionalities, resolving the contradiction between adaptability and complexity

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent segments the protein building blocks by coating them with DNA shells that contain specific sticky end sequences. This segmentation allows different protein-DNA conjugates to be engineered with specific lattice positions and orientations, enabling complex lattice design without compromising protein catalytic activity

Inventive Principle:

Principle #1Segmentation

2Reliability

If proteins are used for therapeutic applications, then enzyme replacement therapy is enabled, but degradation by cellular proteases limits bioavailability

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidprotease resistance

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies a flexible DNA shell around the protein core, creating a protective barrier that shields the protein from cellular proteases while allowing the protein to maintain its therapeutic function. This shell approach significantly improves protease resistance and bioavailability

Inventive Principle:

Principle #30Flexible shells and thin films

Solution Approach 2:

The patent creates composite protein-DNA nanoparticles where the DNA component provides protease resistance and the protein component provides catalytic activity. This composite structure combines the advantages of both materials to achieve both therapeutic efficacy and stability

Inventive Principle:

Principle #40Composite materials

3Duration of action of stationary object

If proteins are stored for prolonged periods, then therapeutic potential is maintained, but aggregation and inactivation occur

Engineering Contradiction:

Improvestorage durationVSAvoidaggregation resistance

Core Design Contradiction:

Duration of action of stationary objectVSStability of the object's composition

Solution Approach 1:

The DNA shell acts as a flexible protective coating that prevents protein aggregation during storage by maintaining steric separation between protein molecules. This shell structure preserves protein stability and prevents inactivation over prolonged storage periods

Inventive Principle:

Principle #30Flexible shells and thin films

4Manufacturing precision

If DNA-mediated assembly is used to create crystalline materials, then well-defined lattice parameters are achieved, but the methods are confined to inorganic nanoparticles

Engineering Contradiction:

Improvelattice parameter definitionVSAvoidbuilding block variety

Core Design Contradiction:

Manufacturing precisionVSAdaptability or versatility

Solution Approach 1:

The patent demonstrates that DNA-mediated assembly is a universal method that can be applied to both inorganic nanoparticles and protein-DNA conjugates. The DNA shell with sticky ends serves as a universal interface that enables precise lattice formation regardless of the core material, achieving both manufacturing precision and building block versatility

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 the predictable assembly of functional proteins into supramolecular materials with defined stoichiometries and relative orientations, maintaining native catalytic functionalities and enhancing bioavailability and stability.

Implementation Method 1

The oligonucleotides on the surface of the protein are sufficiently complementary to a target polynucleotide to hybridize to the target polynucleotide

Methodology Applied

Scientific EffectDNA hybridization:

Data Source

PatentUS12264344B2Protein/oligonucleotide core-shell nanoparticle therapeutics

Publication Date: 2025.04.01 NORTHWESTERN UNIV

AI summary

The present disclosure is directed to core-shell nanoparticles, compositions comprising core-shell nanoparticles, and methods of their use.