Fluorinated Artificial Viral Capsids for Cell Membrane Permeability
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Solution Overview
Problem
Existing artificial viral capsids lack sufficient cell membrane permeability, limiting their effectiveness as drug delivery carriers.
Innovation Solution
Modify the β-annulus peptide of tomato bushy stunt virus with a fluorine-containing compound through a divalent linking group attached to the C-terminus, enhancing the capsid's cell membrane permeability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If artificial viral capsids are formed by self-assembly of β-annulus peptides, then the capsids can encapsulate various substances and be delivered to target cells, but the cell membrane permeability is insufficient
Solution Approach 1:
The patent introduces fluorine atoms into the peptide side chains, changing the chemical composition parameters of the capsid. This parameter change (adding fluorine) directly improves cell membrane permeability while maintaining the self-assembly capability of the β-annulus peptide structure
Solution Approach 2:
The patent creates a composite structure by combining β-annulus peptides with fluorine-containing compounds through linking groups. This composite material approach allows the capsid to retain its encapsulation function while gaining enhanced membrane permeability from the fluorine component
2Reliability
If fluorine-containing compounds are introduced to improve cell membrane permeability, then uptake into cells and escape from endosomes is enhanced, but the complexity of the capsid structure increases
Solution Approach 1:
The patent applies fluorine modification locally at the C-terminus region of the β-annulus peptide rather than throughout the entire structure. This localized modification approach enhances cell uptake efficiency while minimizing the overall structural complexity increase
Solution Approach 2:
The patent uses a divalent linking group as an intermediary between the β-annulus peptide and the fluorine-containing compound. This intermediary simplifies the integration process and reduces the direct complexity of combining the two components
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 capsid exhibits improved cell membrane permeability, making it suitable for use as a pharmaceutical carrier for delivering physiologically active substances.
Implementation Method 1
The β-annulus peptides spontaneously self-assemble in water to form spherical, hollow nanocapsules with diameters of approximately 30-50 nm
Implementation Method 2
compounds having a polyfluoro structure are known to be stable and low in toxicity in vivo, and to be excellent in uptake into cells and escape from endosomes
Data Source
Figure 1(A)~3(B)
Figure 4(A)~6(B)
Figure 7(A)~10
AI summary
The present invention provides an artificial viral capsid modified with a compound containing a fluorine atom. The artificial viral capsid is formed by self-assembly of multiple subunits, wherein the subunit comprises a β-annulus peptide of tomato bushy stunt virus, a group derived from a fluorine-containing compound, and a divalent linking group that links the β-annulus peptide to the group derived from a fluorine-containing compound; and the divalent linking group is linked to a C-terminus of the β-annulus peptide.