Virus-like Particle Delivery of Cyclic Dinucleotides

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Solution Overview

Problem

Cyclic dinucleotides, such as cGAMP, face challenges in efficiently crossing plasma membranes and have limited potency when used without vectors, particularly due to the toxicity of current lipid-based complexes used for delivery.

Innovation Solution

The use of enveloped virus-like particles (VLPs) with a lipoprotein envelope and viral fusogenic glycoproteins to package and deliver cyclic dinucleotides, specifically cGAMP, into cells, optimizing their delivery through fusion with target cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If lipid-based complexes are used to deliver cyclic dinucleotides, then delivery capability is improved, but toxicity increases

Engineering Contradiction:

Improvedelivery capabilityVSAvoidtoxicity

Core Design Contradiction:

Ease of operationVSObject-affected harmful factors

Solution Approach 1:

Virus-like particles serve as an intermediary delivery vehicle that replaces toxic lipid-based complexes. The VLPs with lipoprotein envelopes and fusogenic glycoproteins mediate the delivery of cyclic dinucleotides into cells through fusion mechanisms, achieving effective delivery without the cytotoxicity associated with lipid-based approaches

Inventive Principle:

Principle #24Intermediary (Mediator)

2Device complexity

If cyclic dinucleotides are used without vectors, then simplicity is maintained, but potency is limited

Engineering Contradiction:

Improvesystem simplicityVSAvoidpotency

Core Design Contradiction:

Device complexityVSReliability

Solution Approach 1:

The virus-like particles are designed to self-assemble with cyclic dinucleotides packaged within their structure. The VLPs inherently possess fusogenic properties through their glycoprotein envelopes, enabling them to automatically fuse with target cells and deliver their cargo without requiring additional delivery reagents or complex transfection protocols

Inventive Principle:

Principle #25Self-service

3Productivity

If enveloped virus-like particles are used to deliver cyclic dinucleotides, then delivery efficiency is improved, but manufacturing complexity increases

Engineering Contradiction:

Improvedelivery efficiencyVSAvoidmanufacturing complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The production system is segmented into modular components: expression plasmids for viral structural proteins (capsid, envelope glycoproteins), expression plasmids for cyclic dinucleotide synthase, and co-transfection protocols. This modular approach allows independent optimization of each component and simplifies manufacturing by enabling separate production and assembly of VLP components

Inventive Principle:

Principle #1Segmentation

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

This method enhances the delivery and potency of cGAMP, inducing a robust innate immune response, including an interferon response, by effectively packaging and transferring cGAMP into cells, potentially offering improved vaccine adjuvant properties.

Implementation Method 1

the VLPs need to be enveloped so as to optimize the delivery of cyclic dinucleotides, especially cGAMP, by fusion of VLP with the target cells

Methodology Applied

Scientific EffectViral fusion:

Data Source

PatentUS10010607B2Method for preparing viral particles with cyclic dinucleotide and use of said particles for inducing immune response

Publication Date: 2018.07.03 INSTITUT CURIE

AI summary

The present invention relates to methods for preparing virus-like particles comprising immunogenic cyclic dinucleotides.