Engineered Plant-Derived EVs for mRNA Delivery Without Immune Activation

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Existing nucleic acid-based vaccines, particularly RNA vaccines, face challenges with intracellular delivery, stability, and immunogenicity due to the use of synthetic lipid nanoparticles (LNP), which can induce inflammatory responses and autophagy-lysosomal pathways, leading to inefficient delivery and potential immune system activation or inhibition.

Innovation Solution

Development of non-immunomodulating, engineered plant-derived extracellular vesicles (EVs) loaded with exogenous nucleic acid molecules, characterized by specific membrane properties and size, which deliver antigen-encoding nucleic acids without activating the immune system, ensuring stable delivery and target cell interaction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If synthetic lipid nanoparticles (LNP) are used to deliver mRNA, then mRNA stability and delivery efficiency are improved, but inflammatory responses and immune system activation occur

Engineering Contradiction:

ImprovemRNA delivery efficiencyVSAvoidinflammatory response

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses plant-derived extracellular vesicles as an intermediary carrier to deliver mRNA to target cells. These vesicles naturally interact with cell membranes through membrane fusion rather than endocytosis, avoiding immune system activation while maintaining efficient delivery. The vesicle membrane components (lipids, proteins, carbohydrates) serve as mediators that facilitate direct cytoplasmic delivery of mRNA without triggering inflammatory responses.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the delivery system by changing from synthetic LNP to plant-derived extracellular vesicles, altering key parameters such as membrane composition, surface charge, and interaction mechanism with target cells. This parameter change enables the delivery system to bypass immune recognition pathways while maintaining delivery efficiency.

Inventive Principle:

Principle #35Parameter changes

2Duration of action of moving object

If LNP are used for mRNA delivery, then circulation lifetime is increased, but accumulation in unintended tissues occurs

Engineering Contradiction:

ImproveRNA circulation lifetimeVSAvoidtarget tissue delivery accuracy

Core Design Contradiction:

Duration of action of moving objectVSManufacturing precision

Solution Approach 1:

Plant-derived extracellular vesicles serve as natural intermediaries that exploit existing biological transport pathways. They can naturally cross vascular endothelium and deliver cargo to specific tissues without requiring active targeting mechanisms, thereby achieving both prolonged circulation and accurate tissue delivery.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The extracellular vesicles possess inherent properties that enable them to self-navigate to target tissues. Their natural membrane composition and size allow them to passively cross endothelial barriers and accumulate in specific tissues through physiological processes rather than requiring external guidance mechanisms.

Inventive Principle:

Principle #25Self-service

3Power

If LNP are used for mRNA delivery, then protein expression is enhanced, but autophagy-lysosomal pathway activation occurs

Engineering Contradiction:

Improveprotein expression levelVSAvoidautophagy-lysosomal pathway activation

Core Design Contradiction:

PowerVSObject-generated harmful factors

Solution Approach 1:

The patent uses extracellular vesicles as intermediaries that deliver mRNA directly to the cytoplasm through membrane fusion, bypassing the endocytic pathway that would otherwise lead to lysosomal degradation. This intermediary mechanism ensures that mRNA reaches the translation machinery without being degraded by autophagy-lysosomal pathways.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

Instead of using endocytosis (which leads to lysosomal degradation), the patent employs reverse endocytosis or direct membrane fusion mechanisms. The extracellular vesicles fuse with the target cell membrane and release mRNA directly into the cytoplasm, inverting the conventional delivery pathway to avoid degradation.

Inventive Principle:

Principle #13The other way round (Inversion)

4Object-affected harmful factors

If plant-derived EVs are used for vaccine delivery, then immune system activation is avoided, but delivery efficiency must be maintained

Engineering Contradiction:

Improveimmune system activationVSAvoiddelivery efficiency

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

Plant-derived extracellular vesicles act as natural intermediaries that are inherently recognized by cell membranes through conserved membrane fusion mechanisms. This intermediary role allows them to deliver mRNA efficiently without triggering immune responses, as they exploit fundamental cellular processes rather than foreign recognition pathways.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20250281599A1Composition comprising engineered plant-derived extracellular vesicles and use thereof as a vaccine

Publication Date: 2025.09.11 EV BIOSOLUTIONS SPA

AI summary

A method for treatment or prophylaxis of a disease in a subject involving administering to the subject a vaccine composition including non-immunomodulating, engineered, plant-derived extracellular vesicles (EVs), is provided. The Evs are loaded with an exogenous nucleic acid molecule encoding a protein antigen. The disease is an infectious disease or cancer. A method for the preparation of the vaccine composition, which makes use of one or more polycationic substances and one or more sugar molecules is also provided.