Peptide Capsomers for Monodisperse Nucleic Acid Delivery
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Solution Overview
Problem
Current methods for preparing nanostructures through self-assembly lack control over the dimensions and stability of one-dimensional objects, particularly for the delivery of nucleic acids, resulting in polydisperse and biologically inactive complexes.
Innovation Solution
The development of peptide segments with specific domains that self-assemble into capsomers, which can encapsulate charged compounds like DNA, forming monodisperse filamentous nanostructures with controlled dimensions and stability, utilizing a coiled-coil structure and a water-soluble polymer to enhance rigidity and biocompatibility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If self-assembly methods are used to prepare one-dimensional nanostructures, then the formation of nanostructures is achieved, but control over dimensions and stability is lost resulting in polydisperse complexes
Solution Approach 1:
The self-assembling molecule is divided into distinct functional domains: a rigid rod domain for structural control and dimension definition, a coiled-coil domain for controlled oligomerization into capsomers, and a hydrophobic domain for nucleation control. This segmentation allows each domain to independently control specific aspects of assembly, achieving both dimensional precision and stability.
Solution Approach 2:
The patent utilizes changes in physical and chemical parameters including pH, ionic strength, and temperature to control the self-assembly process. By adjusting these parameters, the system transitions from monomeric rods to oligomeric capsomers with controlled dimensions, achieving monodispersity and stability simultaneously.
2Manufacturing precision
If control of nucleation and kinetics is used for cylindrical micelles, then growth control is improved, but the nanostructures remain polydisperse due to supramolecular living polymerization
Solution Approach 1:
The rigid rod domain is pre-designed with specific length and stiffness parameters before assembly occurs. This preliminary structural definition sets the maximum dimension of the final capsomer, ensuring monodispersity. The coiled-coil domain is also pre-configured to form a specific number of oligomers, controlling the assembly stoichiometry in advance.
3Ease of manufacture
If peptide amphiphiles form micrometer long nanofibers, then self-assembly occurs, but the structures lack controlled dimensions and are not suitable for nucleic acid delivery
Solution Approach 1:
The patent creates a composite self-assembling molecule combining rigid rod characteristics for dimensional control with coiled-coil characteristics for controlled oligomerization. This composite structure prevents uncontrolled fiber elongation while maintaining self-assembly capability, producing discrete capsomers with defined dimensions suitable for nucleic acid encapsulation.
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
This approach enables the formation of highly homogeneous, stable nanostructures capable of efficient nucleic acid delivery, with controlled morphology and dimensions, suitable for gene and siRNA delivery, and exhibits electronic properties such as semiconductivity.
Implementation Method 1
In aqueous solution, coassembly was favored by hydrophobic collapse resulting in the formation of non-spherical core-shell supramolecular aggregates with controlled dimensions
Implementation Method 2
the second domain comprises an amino acid sequence with a coiled-coil structure
Implementation Method 3
the third domain comprises a water soluble polymer and is positioned at a second terminus of the second domain
Data Source
AI summary
The present disclosure is directed to the preparation of nanostructures by the encapsulation of a charged compound with individual self-assembled unit nano structures.