Polymer Nanoparticle and DNA Origami Delivery for Large Gene Payloads

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Solution Overview

Problem

Current gene delivery systems, including adeno-associated viruses (AAVs) and non-viral systems like liposomes, struggle with delivering large genetic payloads or multiple payloads to specific tissues while avoiding immune responses and ensuring stability, leading to inefficiencies and safety concerns.

Innovation Solution

Development of polymer nanoparticle and DNA nanostructure compositions, such as RAFT polymer and DNA origami, which are biocompatible, programmable, and capable of immune evasion, enabling targeted and controlled delivery of large or multiple genetic payloads.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If adeno-associated viruses (AAVs) are used for genetic medicine delivery, then delivery efficiency to specific tissues is improved, but the ability to deliver large genetic payloads or multiple payloads is limited and immune responses are triggered

Engineering Contradiction:

Improvedelivery efficiencyVSAvoidpayload capacity

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent segments the delivery system into multiple components: a capsid protein component for targeted delivery and a separate nucleic acid component for the genetic payload. This segmentation allows the use of smaller, more versatile delivery vehicles that can avoid immune responses while maintaining tissue-specific delivery capability, and enables the delivery of large or multiple payloads by separating the delivery mechanism from the payload capacity constraints

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent creates a universal delivery platform using modified capsid proteins that can deliver various types of nucleic acid payloads (single or multiple, large or small) to different tissue targets. The capsid protein component serves multiple functions: providing tissue-specific targeting, protecting the nucleic acid payload, and enabling delivery without triggering immune responses, making the system adaptable to different genetic medicine applications

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If adeno-associated viruses (AAVs) are used for genetic medicine delivery, then targeted delivery to specific tissues is achieved, but unwanted immune responses including anti-AAV antibodies are generated

Engineering Contradiction:

Improvetargeted deliveryVSAvoidimmune responses

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses modified capsid proteins that are designed to be transient and non-immunogenic. These capsid proteins serve their delivery function and are then naturally degraded without triggering long-term immune responses or memory formation, allowing for potential repeat administrations if needed. The modified capsid proteins act as disposable delivery vehicles that complete their function without causing harmful immune effects

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent introduces modified capsid proteins as intermediary carriers between the delivery system and the target tissues. These intermediaries provide the necessary targeting and delivery functions while being engineered to avoid direct recognition by the immune system, thus mediating the delivery process without triggering immune responses

Inventive Principle:

Principle #24Intermediary (Mediator)

3Ease of manufacture

If current non-viral gene delivery systems like liposomes are used, then ease of manufacture is improved, but biocompatibility is poor and enzymatic degradation occurs

Engineering Contradiction:

Improvemanufacturing simplicityVSAvoidbiocompatibility

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent creates composite delivery systems by combining capsid proteins with nucleic acid payloads. The capsid protein component provides biocompatibility and protection from enzymatic degradation, while the nucleic acid component provides the therapeutic payload. This composite structure maintains ease of manufacture through modular assembly while dramatically improving biocompatibility and stability in biological environments

Inventive Principle:

Principle #40Composite materials

4Ease of manufacture

If current non-viral gene delivery systems are used, then ease of manufacture is improved, but the ability to package multiple large payloads is limited

Engineering Contradiction:

Improvemanufacturing simplicityVSAvoidmultiple payload capacity

Core Design Contradiction:

Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent segments the payload delivery into multiple nucleic acid components that can be independently packaged with capsid proteins. This segmentation allows for the delivery of multiple large payloads (such as CRISPR/Cas9 systems with multiple genes) while maintaining modular manufacturing processes. Each capsid-nucleic acid complex can be manufactured separately and then combined, preserving manufacturing simplicity while enabling multiple payload delivery

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS20260014186A1Polymer nanoparticle and DNA nanostructure compositions and methods for non-viral delivery

Publication Date: 2026.01.15 BATTELLE MEMORIAL INST

AI summary

The invention relates to polymer nanoparticle and DNA nanostructure delivery compositions for non-viral delivery, and methods therefor. More particularly, the invention relates to polymer nanoparticle delivery compositions, such as reversible addition-fragmentation chain transfer (RAFT) polymer compositions, and DNA nanostructure delivery compositions, such as DNA origami compositions, for the delivery of more than one payload, or for the delivery of a nucleic acid construct payload of 3 kB or more, and methods therefor.