Plasma Membrane Bleb Nanovesicles for Targeted Protein Delivery

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Solution Overview

Problem

Current methods for protein delivery, including nanoparticles and extracellular vesicles, face challenges such as heterogeneity, low productivity, and difficulty in targeting specific cells, leading to toxicity and reduced therapeutic efficacy, especially for enveloped viruses where traditional virus-like particle vaccines have not been successful due to complex biosynthetic processes.

Innovation Solution

The development of plasma membrane bleb-based nanovesicles expressing immunomodulatory or targeting proteins, produced by establishing cell lines that overexpress these proteins and using bleb-inducing agents like N-ethyl maleimide to induce and separate nanovesicles, which are then purified and sized to enhance homogeneity and targeting capabilities.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If extracellular vesicles are used for protein delivery, then targeting capability is improved, but heterogeneity and low productivity occur leading to difficulty in therapeutic application

Engineering Contradiction:

Improvetargeting capabilityVSAvoidproductivity

Core Design Contradiction:

Adaptability or versatilityVSProductivity

Solution Approach 1:

The invention segments the complex biosynthetic pathway of extracellular vesicles by using a simplified alternative approach: transfecting plasmids directly into cells to express target proteins, then inducing plasma membrane blebbing to form nanovesicles. This segmentation bypasses the complex natural vesicle formation process while retaining the desired targeting capability through surface-expressed proteins.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention changes the production parameters by using chemical induction (N-ethyl maleimide treatment) to trigger plasma membrane blebbing and nanovesicle formation, rather than relying on the natural, complex biosynthetic pathway of extracellular vesicles. This parameter change enables controlled, high-yield production of homogeneous nanovesicles with consistent size and protein distribution.

Inventive Principle:

Principle #35Parameter changes

2Duration of action of moving object

If synthetic nanoparticles are used to increase protein half-life, then pharmacokinetics are improved, but toxicity occurs due to accumulation in non-target tissues

Engineering Contradiction:

Improveprotein half-lifeVSAvoidtoxicity

Core Design Contradiction:

Duration of action of moving objectVSObject-affected harmful factors

Solution Approach 1:

The invention applies local quality by expressing specific targeting proteins on the surface of nanovesicles, enabling them to recognize and bind to specific target cells or tissues. This localized targeting capability ensures that the nanovesicles deliver their protein cargo specifically to the intended destination, preventing accumulation in non-target tissues and reducing toxicity while maintaining extended half-life.

Inventive Principle:

Principle #3Local quality

3Adaptability or versatility

If enveloped viruses are used for vaccine development, then structural diversity and immune evasion are improved, but complex biosynthetic pathways cause heterogeneity and low productivity

Engineering Contradiction:

Improvestructural diversityVSAvoidbiosynthetic pathway complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The invention extracts the essential functional components of enveloped viruses (the plasma membrane structure and surface-expressed proteins) while leaving behind the complex biosynthetic machinery. By using plasmid transfection to express viral proteins on the cell surface and then inducing plasma membrane blebbing, the invention creates simplified virus-like nanovesicles that retain structural diversity and immune evasion capabilities without the complexity of full viral replication cycles.

Inventive Principle:

Principle #2Taking out (Extraction)

Data Source

PatentUS20240382582A1Immunomodulatory proteins- or targeting proteins-expressing nanovesicles, methods of preparing the nanovesicle and use thereof

Publication Date: 2024.11.21 POSTECH ACADEMY INDUSTRY FOUNDATION

AI summary

The present invention relates to nanovesicles which express immunomodulatory proteins or targeting proteins, methods for preparing the same and uses thereof. More specifically, the present invention provides plasma membrane bleb-based nanovesicles which are prepared more homogeneously than existing plasma membrane bleb-based nanovesicles, by using cell lines expressing various immunomodulatory proteins or targeting proteins in the plasma membrane as materials, methods for preparing the nanovesicles, pharmaceutical compositions including the nanovesicles, methods for inducing immunity using the nanovesicles and methods for signal transduction or targeting using the nanovesicles.