Peptide-Functionalized DNA Nanostructures for Endolysosomal Escape
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Solution Overview
Problem
Current DNA nanostructures face challenges in cellular uptake and endolysosomal escape efficiency due to limited control over size, shape, and surface chemistry, as well as the impact of the protein corona formed in biological fluids, which hampers their clinical translation.
Innovation Solution
Functionalization of DNA nanostructures with an endolysosomal escape peptide, such as the lysine10 (K10) peptide flanked by aurein 1.2, to enhance cellular uptake and stability, utilizing electrostatic interactions and a specific nitrogen/phosphate ratio for coating, and assessing the protein corona's effect on endolysosomal escape efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If DNA nanostructures are functionalized with endolysosomal escape peptides to enhance cellular uptake, then endolysosomal escape efficiency is improved, but the complexity of the nanostructure increases
Solution Approach 1:
The patent combines DNA nanostructures with endolysosomal escape peptides to create a composite material that leverages the structural precision of DNA and the membrane-disrupting capability of peptides. This composite approach enables endolysosomal escape functionality while maintaining the modular and controllable nature of DNA-based platforms.
Solution Approach 2:
The endolysosomal escape peptides are specifically positioned on the surface of the DNA nanostructure, allowing the core DNA structure to maintain its structural integrity and programmability while only the surface regions acquire the membrane-disrupting functionality. This localized functionalization minimizes overall structural complexity.
2Stability of the object's composition
If the protein corona is allowed to form on DNA nanostructures in biological fluids, then the nanostructures become more stable, but the endolysosomal escape efficiency is reduced
Solution Approach 1:
The patent pre-coats the DNA nanostructures with endolysosomal escape peptides before introducing them to biological fluids. This preliminary functionalization ensures that the peptides are already positioned on the nanostructure surface to facilitate endolysosomal escape, even though a protein corona will subsequently form. The pre-attached peptides can still exert their membrane-disrupting function despite the presence of adsorbed proteins.
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 peptide-functionalized DNA nanostructures demonstrate enhanced endolysosomal escape without cytotoxicity and maintain stability in lysosomal compartments, with cellular uptake efficiency linearly dependent on cell size, providing a foundation for optimized delivery vehicles.
Implementation Method 1
the endolysosomal escape peptide coating binds the DN through electrostatic interactions at a nitrogen/phosphate ratio of about 0.8 to about 1.5
Data Source
AI summary
Described herein are DNA nanostructures (DN) functionalized with proteins and methods for cellular uptake. Cellular uptake of such DNs is linearly dependent on the cell size. The protein corona determines the endolysosomal vesicle escape efficiency of DNs coated with an endosome escape peptide.