Cross-linked TRAP-cage for stoichiometry-controlled cargo encapsulation
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Solution Overview
Problem
Current methods for loading proteins or therapeutics into TRAP-cages are not facile and lack control over stoichiometry, making it challenging to effectively package and deliver guest cargo for biotechnological and medical applications.
Innovation Solution
The development of an artificial TRAP-cage comprising a selected number of TRAP rings held together by cross-linkers, such as molecular or atomic metal cross-linkers, with a programmable opening mechanism, allowing for controlled encapsulation and release of guest cargo, including proteins, nucleic acids, and nanoparticles, using techniques like genetic fusion, SpyCatcher/SpyTag conjugation, and covalent bonding.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If traditional loading methods are used for TRAP-cages, then the process is simple, but the stoichiometry control and loading efficiency are poor
Solution Approach 1:
The patent applies preliminary action by pre-modifying TRAP rings with cross-linkable groups (such as maleimide groups) before cage assembly. This allows controlled cross-linking of TRAP rings to form stable cages with precise stoichiometry (e.g., 12-ring or 24-ring cages) before cargo loading, ensuring manufacturing precision without requiring complex loading processes later
Solution Approach 2:
The patent uses molecular cross-linkers (such as BS3, DMTMM, or maleimide-containing compounds) as intermediaries to mediate the assembly of TRAP rings into stable cages. These cross-linkers provide controlled stoichiometry by forming defined numbers of bonds between TRAP rings, enabling precise cage construction while simplifying the overall loading process
2Stability of the object's composition
If TRAP-cages are made highly stable under harsh conditions, then they maintain structural integrity, but they become difficult to disassemble for cargo release
Solution Approach 1:
The patent applies dynamics by using cross-linkers with controllable bond stability. The cross-linked TRAP cages maintain high stability under harsh conditions (pH, temperature, proteases) during circulation, but can be dynamically disassembled when needed by adding specific reagents (such as reducing agents for disulfide cross-linkers or hydroxylamine for hydrazone cross-linkers), enabling controlled cargo release
Solution Approach 2:
The patent uses parameter changes by selecting cross-linkers whose bond stability can be changed by specific environmental parameters. For example, pH-sensitive cross-linkers remain stable at physiological pH but disassemble at acidic pH, or redox-sensitive cross-linkers remain stable in oxidizing conditions but disassemble in reducing conditions, allowing controlled disassembly without compromising overall cage stability
3Volume of stationary object
If the TRAP-cage lumen is made larger to accommodate bigger cargo, then the cargo capacity increases, but the structural integrity and stability decrease
Solution Approach 1:
The patent applies segmentation by constructing cages from multiple discrete TRAP rings (e.g., 12 or 24 rings) that are cross-linked together. This modular approach allows the cage to accommodate larger cargo volumes while maintaining structural integrity through the distributed cross-linking network, as each TRAP ring-unit contributes to the overall strength
Solution Approach 2:
The patent uses composite materials by combining TRAP protein rings with synthetic or biological cross-linkers to create hybrid cage structures. This composite approach enables the construction of larger, more voluminous cages that maintain strength through the synergistic combination of protein subunits and cross-linking agents, accommodating bigger cargo while preserving structural integrity
4Reliability
If cross-linkers are used to stabilize TRAP rings, then the cage stability increases, but the flexibility and programmability for controlled opening decrease
Solution Approach 1:
The patent uses parameter changes by selecting cross-linkers with specific environmental sensitivities (pH, redox potential, temperature, light). This allows the cage to maintain high stability under normal conditions while being programmably opened by changing specific parameters (e.g., adding reducing agent, changing pH, or exposing to light), thus maintaining both reliability and adaptability
Solution Approach 2:
The patent uses cleavable cross-linkers that act as intermediaries with built-in triggering mechanisms. These cross-linkers mediate stable cage assembly but contain labile bonds that can be selectively cleaved by specific reagents or stimuli, providing programmable opening capability while maintaining overall cage stability during circulation
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
Enables robust, stoichiometry-controllable internal loading and release of cargo, maintaining stability under harsh conditions while facilitating intracellular delivery and targeting specific therapeutic agents to desired locations, enhancing the potential for biotechnological and medical applications.
Implementation Method 1
cross-linkers are molecular cross linkers or atomic metal cross linkers. Preferably the TRAP rings are linked by gold or DTME
Implementation Method 2
the TRAP rings are linked by gold or DTME
Data Source
AI summary
The present invention provides an artificial TRAP-cage comprising a selected number of TRAP rings and encapsulated therein a guest cargo.