Exosome Biotherapeutic Delivery via Electroporation

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Solution Overview

Problem

Biotherapeutic agents like proteins and peptides, such as antibodies, face challenges in delivery due to rapid clearance, lack of organ-specific distribution, and low cellular uptake when administered naked, necessitating a specialized delivery vehicle.

Innovation Solution

Loading exosomes with exogenous proteins or peptides, including antibodies, and using them as targeted delivery vehicles, which can be derived from immature dendritic cells and loaded via electroporation or cationic liposome transfection, to enhance stability and specificity of biotherapeutic delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If biotherapeutic agents are administered in naked form, then administration is simple, but clearance is rapid and cellular uptake is low

Engineering Contradiction:
Improveadministration simplicityVSAvoiddelivery efficacy
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent uses exosomes as intermediary delivery vehicles to transport biotherapeutic agents. These exosomes are engineered to carry therapeutic proteins or peptides while protecting them from rapid clearance and facilitating cellular uptake, thus resolving the contradiction between simple administration and effective delivery.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the physical and chemical parameters of biotherapeutic agents by encapsulating them within exosomes. This changes their pharmacokinetic properties, extending circulation half-life and enhancing cellular internalization, thereby improving delivery efficacy without complicating the administration process.

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If biotherapeutic agents are administered naked, then distribution is non-specific, but administration method is simple

Engineering Contradiction:
Improveadministration simplicityVSAvoidorgan-specific distribution
Core Design Contradiction:
Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent introduces targeting moieties on exosome surfaces to confer organ-specific distribution properties. By modifying specific regions of the exosome with targeting ligands, the system achieves selective delivery to desired tissues while maintaining simple administration through intravenous injection.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

Exosomes serve as intermediary carriers that can be engineered with specific targeting capabilities. These engineered exosomes mediate the transport of biotherapeutics to specific organs, providing adaptability and versatility in distribution patterns while keeping the administration process simple.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If exosomes are loaded with exogenous protein by electroporation, then loading efficiency is high, but process complexity increases

Engineering Contradiction:
Improveloading efficiencyVSAvoidloading process complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent employs electroporation to temporarily alter the membrane permeability parameters of exosomes, enabling efficient loading of exogenous proteins. By controlling electrical field parameters, the method achieves high loading efficiency while managing process complexity through optimized protocol parameters.

Inventive Principle:
Principle #35Parameter changes

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

Exosomes provide protected and stable delivery of biotherapeutics, enabling efficient and specific targeting of tissues, reducing immune response and potential for drug resistance, while avoiding hepatic cells and improving therapeutic efficacy.

Implementation Method 1

Exosomes are small membrane-bound vesicles (30-100 nm) of endocytic origin that are released into the extracellular environment

Methodology Applied
Scientific EffectPhysical containment: Physical Containment

Implementation Method 2

loading the exosomes with protein and/or peptide by electroporation

Methodology Applied
Scientific EffectElectroporation:

Implementation Method 3

loading the exosomes with protein and/or peptide by transfection, using a cationic liposome transfection agent

Methodology Applied
Scientific EffectElectrostatic interaction:

Data Source

PatentUS11103586B2Exosomes for delivery of biotherapeutics
Publication Date: 2021.08.31 OXFORD UNIVERSITY INNOVATION LTD
  • US11103586B2 patent drawing
  • US11103586B2 patent drawing

AI summary

The present invention relates to exosomes, loaded with biotherapeutic protein and/or peptide and methods of producing them and to the use of such exosomes for delivering protein and/or peptide in vivo, in particular the use of such exosomes in methods of therapy.