Engineered Microbial Vesicles for Targeted mRNA Delivery

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Solution Overview

Problem

Current mRNA therapeutics face challenges in delivering therapeutic proteins to specific targets with high efficiency and durability, as lipid nanoparticles (LNPs) accumulate in the liver, activate innate immunity, and face barriers in the gastrointestinal tract, while existing extracellular vesicle (EV) engineering strategies lack robustness and scalability.

Innovation Solution

Development of AI-guided engineered microbial vesicles using non-bacterial proteins for anchoring, combined with an automated analytical system (TIMES) to enhance target-specific delivery, leveraging gram-negative bacteria like E. coli and spirulina for safe and cost-effective production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If lipid nanoparticles are used for mRNA delivery, then delivery efficiency is improved, but liver accumulation and immune activation occur

Engineering Contradiction:

Improvedelivery efficiencyVSAvoidliver accumulation and immune activation

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent uses bacterial membrane vesicles as intermediary carriers to deliver mRNA therapeutics. These vesicles serve as a mediator between the mRNA payload and target cells, avoiding the harmful effects of lipid nanoparticles while maintaining delivery efficiency. The bacterial vesicles can be engineered with specific surface proteins for targeted delivery without triggering the same immune responses as LNPs.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the physical and chemical parameters of the delivery vehicle by using bacterial membrane vesicles instead of lipid nanoparticles. This includes changing the material composition from synthetic lipids to bacterial membrane components, altering the surface properties through protein engineering, and modifying the size and structure parameters to achieve targeted delivery with reduced immunogenicity.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If existing extracellular vesicle engineering strategies are used, then scalability is improved, but robustness and target-specific delivery are insufficient

Engineering Contradiction:

ImprovescalabilityVSAvoidrobustness and target-specific delivery

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent segments the extracellular vesicle engineering approach into distinct functional modules: bacterial vesicle production for scalability, engineered surface proteins for target-specific binding, and customizable payload compartments. This modular segmentation allows each component to be optimized independently while maintaining overall system robustness and reliability.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent creates a universal platform using bacterial membrane vesicles that can be engineered to perform multiple functions: targeted delivery to different cell types through various surface protein configurations, delivery of different mRNA payloads, and potential combination with other therapeutic mechanisms. This multi-functionality enhances both robustness and adaptability across different therapeutic applications.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20260027229A1Artificial intelligence-guided protein design for nanovesicle analysis and engineering

Publication Date: 2026.01.29 ACCURE HEALTH INC

AI summary

This disclosure provides an engineered delivery system, including a bacterial membrane vesicle derived from bacteria and one or more non-bacterial proteins for anchoring to the bacterial membrane vesicle.