Engineered Human-Endogenous Virus-Like Particles for Safer Cell Delivery
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Solution Overview
Problem
Current methods for delivering proteins, nucleic acids, and chemicals into the cytosol of living cells are inefficient, unsafe, and often result in immunogenic responses due to the use of conventional lipid/gold nanoparticles and viral particle-based delivery systems, which can integrate unwanted DNA and exhibit off-target effects.
Innovation Solution
Development of engineered human-endogenous virus-like particles (heVLPs) composed of a phospholipid bilayer and human-derived components, excluding non-human gag and pol proteins, capable of packaging and delivering DNA, RNA, proteins, and chemicals, utilizing human-endogenous GAG proteins for efficient cellular uptake and minimizing immunogenicity.
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 immunogenic viral components (gag and pol proteins from non-human viruses) from the delivery system while retaining the essential virus-like particle structure and delivery functionality. This creates heVLPs that maintain efficient cellular delivery capabilities without the harmful immunogenic elements that cause immune responses and off-target effects.
Solution Approach 2:
The patent changes the composition parameters of the delivery particle by substituting non-human viral proteins with human-derived components. This parameter change maintains the structural and functional properties needed for efficient delivery while eliminating the immunogenicity associated with foreign viral proteins.
2Ease of operation
If conventional lipid/gold nanoparticles are used, then delivery capability is achieved, but safety and efficiency are reduced
Solution Approach 1:
The patent creates a composite particle structure combining human-derived GAG proteins with phospholipid bilayers to form heVLPs. This composite approach integrates the biocompatibility and safety of human-derived components with the efficient delivery capabilities of virus-like structures, overcoming the limitations of conventional lipid or gold nanoparticles.
Solution Approach 2:
The heVLPs utilize human-endogenous GAG proteins that naturally facilitate cellular uptake and delivery processes. These human-derived components self-organize into functional particles that automatically perform the delivery function without requiring external assistance or complex formulation procedures.
3Ease of manufacture
If non-human gag and pol proteins are used in VLPs, then particle formation is achieved, but immunogenicity increases
Solution Approach 1:
The patent applies homogeneity by using human-derived GAG proteins throughout the particle structure instead of mixing human and non-human components. This uniform composition of human-derived materials ensures biocompatibility and eliminates immunogenicity while maintaining the ability to form functional virus-like particles.
Data Source
AI summary
Human-derived virus-like particles (heVLPs), comprising a membrane comprising a phospholipid bilayer with one or more HERV-derived envelope proteins on the external side; one or more HERV-derived GAG proteins in the heVLP core, and a cargo molecule, e.g., a biomolecule and/or chemical cargo molecule, disposed in the core of the heVLP on the inside of the membrane, wherein the heVLP does not comprise a gag protein, except for gag proteins that are encoded in the human genome or gag proteins that are encoded by a consensus sequence that is derived from gag proteins found in the human genome, and methods of use thereof for delivery of the cargo molecule to cells.