eVLP Cargo Delivery Without Gag/Pol for Safer Cell Entry
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Solution Overview
Problem
Current methods for delivering cargo such as proteins, nucleic acids, and chemicals into the cytosol of living cells are inefficient, unsafe, and often result in immunogenicity and off-target effects due to the use of viral components in conventional delivery systems.
Innovation Solution
Enhanced virus-like particles (eVLPs) composed of a phospholipid bilayer with virally-derived glycoproteins and a cargo core, lacking gag and pol proteins, which utilize human-derived phospholipid bilayer recruitment domains to package and deliver a variety of biomolecules, including nucleic acids and proteins, without requiring chemical-based dimerizers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional viral particle-based delivery systems are used, then delivery efficiency is improved, but immunogenicity and off-target effects increase
Solution Approach 1:
The patent extracts and removes the harmful viral components (gag and pol proteins) from the delivery system while retaining the beneficial envelope glycoproteins that enable cellular entry. This creates an enhanced VLP system that maintains delivery efficiency without the immunogenicity caused by complete viral particles.
Solution Approach 2:
The patent applies local quality by selectively removing only the harmful portions (gag and pol proteins) while preserving the functional envelope glycoproteins. This localized modification allows the system to maintain its entry function while eliminating harmful effects.
2Ease of operation
If viral components are used in delivery systems, then cellular entry capability is improved, but safety decreases
Solution Approach 1:
The patent extracts the dangerous viral structural proteins (gag and pol) while keeping the safe and functional envelope glycoproteins that mediate cellular entry. This results in a safer delivery system that retains the desired cellular entry capability.
Solution Approach 2:
The envelope glycoproteins serve as intermediaries that enable cellular entry without the harmful effects of complete viral particles. These glycoproteins mediate the interaction between the delivery system and target cells while the removed gag and pol proteins eliminate safety concerns.
3Productivity
If chemical-based dimerizers are used, then cargo packaging is improved, but complexity and toxicity increase
Solution Approach 1:
The patent enables the VLP system to self-assemble and self-package cargo through the natural properties of the envelope glycoproteins and phospholipid bilayer recruitment domains, eliminating the need for external chemical dimerizers. This self-organizing capability reduces system complexity and removes toxic chemical components.
Solution Approach 2:
The patent replaces chemical-based dimerization systems with a biological self-assembly mechanism driven by phospholipid bilayer recruitment domains. This substitution eliminates the need for toxic chemicals while maintaining cargo packaging efficiency.
Data Source
AI summary
Enhanced virus-like particles (eVLPs), comprising a membrane comprising a phospholipid bilayer with one or more virally-derived glycoproteins on the external side; and a cargo disposed in the core of the eVLP on the inside of the membrane, wherein the eVLP does not comprise an exogenous gag/pol protein, and methods of use thereof for delivery of the cargo to cells.