Membrane-Engineered Capsids for Antibody-Evasive Biomolecule Delivery
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Solution Overview
Problem
Existing virus delivery methods, particularly for non-enveloped viruses, face challenges in efficiently entering target cells and avoiding neutralization by antibodies, as they lack membrane fusion proteins and are susceptible to immune recognition.
Innovation Solution
Modified capsid proteins incorporating a membrane binding element and an ESCRT-recruiting element, heterologous to the capsid forming protein, enable quasi-enveloped virus-like nanocarriers that bud into membrane vesicles, allowing ESCRT-dependent release and efficient cellular entry.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If non-enveloped viruses are used for delivery, then they can enter cells through membrane disruption, but they are susceptible to antibody recognition and neutralization
Solution Approach 1:
The patent creates a hybrid structure combining non-enveloped virus capsids with a lipid membrane envelope. The capsid retains the membrane disruption capability for cellular entry, while the external lipid membrane provides camouflage from the immune system, allowing the virus to evade antibody recognition. This composite structure merges the advantages of both enveloped and non-enveloped viruses.
Solution Approach 2:
The patent incorporates a lipid membrane envelope around the capsid, creating a flexible protective shell. This thin film structure allows the virus to maintain its infectious capabilities while gaining protection from immune recognition. The membrane envelope can deform and interact with cell membranes, facilitating entry while shielding the immunogenic capsid proteins.
2Object-affected harmful factors
If enveloped viruses are used for delivery, then they can evade antibody recognition through membrane coating, but they require viral fusion proteins that complicate the structure
Solution Approach 1:
The patent extracts only the essential membrane envelope component from enveloped viruses, separating it from the complex viral fusion machinery. By using a simplified lipid membrane without requiring viral fusion proteins, the design achieves immune evasion while reducing structural complexity and eliminating the need for complex fusion mechanisms.
Solution Approach 2:
The patent introduces an intermediary lipid membrane between the capsid and the external environment. This membrane acts as a mediator that provides immune evasion capabilities without requiring direct interaction between viral proteins and host cell membranes, thereby simplifying the entry mechanism and reducing overall structural complexity.
3Object-affected harmful factors
If quasi-enveloped viruses are created with membrane vesicles, then antibody recognition is reduced, but the release mechanism requires ESCRT pathway dependency
Solution Approach 1:
The patent incorporates ESCRT recruitment elements directly into the capsid structure, enabling the virus to autonomously recruit host ESCRT machinery for membrane scission and release. This self-service mechanism allows the virus to exploit existing cellular pathways without requiring complex viral proteins, achieving efficient release while maintaining relatively simple viral structure.
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
The modified capsids effectively deliver cargo into target cells while evading antibody recognition, enhancing delivery efficiency and stability.
Implementation Method 1
a membrane binding element
Implementation Method 2
an ESCRT-recruiting element, wherein at least one of the membrane binding element and the ESCRT-recruiting element is heterologous to the capsid forming protein
Data Source
AI summary
Disclosed herein are modified capsid proteins comprising a capsid forming protein, a membrane binding element and an ESCRT-recruiting element, wherein at least one of the membrane binding element and the ESCRT-recruiting element is heterologous to the capsid forming protein. Disclosed are capsids comprising a plurality of modified capsid proteins. Disclosed are multimeric assemblies comprising a plurality of capsids within a membrane. Also disclosed are modified non-enveloped viruses comprising a capsid wherein the capsid comprises a plurality of modified capsid proteins, wherein the plurality of modified capsid proteins comprise a capsid forming protein, a membrane binding element and an ESCRT-recruiting element, wherein at least one of the membrane binding element and the ESCRT-recruiting element is heterologous to the modified capsid protein, wherein the capsid forming protein is a capsid forming protein of a non-enveloped virus.