Ligand Operable Protein Cages for Controlled Disassembly
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Solution Overview
Problem
Existing self-assembling protein cages are difficult to disassemble under physiological conditions, as they require non-specific denaturants such as acids, bases, salts, solvents, and heat, which are not suitable for many applications.
Innovation Solution
The development of Ligand Operable Protein Cages (LOCs) that comprise subunits with at least 90% sequence identity to known protein cages, fused with a given binder covalently attached to the N-terminus or C-terminus of the subunits. Upon binding of the cognate ligand, the non-covalent interactions between subunits are disrupted, causing the protein cage to open and release any passenger molecules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional denaturants (acids, bases, salts, solvents, heat) are used to disassemble protein cages, then the protein cages can be disassembled, but the conditions are non-specific and unsuitable for physiological applications
Solution Approach 1:
The patent introduces a binder as an intermediary component that specifically recognizes and binds to a ligand, triggering cage disassembly. This mediator enables specific disassembly under physiological conditions without requiring harsh denaturants, resolving the contradiction between specificity and physiological compatibility
Solution Approach 2:
The invention changes the disassembly mechanism from non-specific denaturation to specific ligand-binding triggered conformational changes. By modifying the cage structure to include ligand-binding domains, the disassembly parameters shift from harsh chemical/physical conditions to mild physiological conditions with specific molecular recognition
2Ease of operation
If harsh denaturants are applied to disassemble protein cages, then disassembly is achieved, but the method lacks specificity and cannot target particular cages
Solution Approach 1:
The binder acts as a specific intermediary that recognizes unique ligand features, enabling targeted disassembly of specific cage populations. This mediator provides both ease of operation through controlled triggering and reliability through specific molecular recognition
Solution Approach 2:
The invention extracts the disassembly trigger from general denaturants to a specific ligand-binding event. By taking out the specificity requirement from the disassembly mechanism, the system achieves both ease of controlled operation and high reliability through selective ligand recognition
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
LOCs enable specific and controlled disassembly of protein cages under physiological conditions, allowing for targeted delivery or release of passenger molecules such as therapeutic agents, diagnostic reagents, or detectable labels.
Implementation Method 1
Upon binding of the cognate ligand, the non-covalent interactions between subunits are disrupted
Implementation Method 2
a plurality of subunits bound together by non-covalent interactions
Data Source
AI summary
Disclosed herein are protein cages that can be assembled and disassembled on command and methods and compositions thereof.