Lactoferrin-Derived Peptides for Rapid Endolysosomal Cargo Release
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Solution Overview
Problem
Current cell-penetrating peptides (CPPs) face challenges in rapidly releasing cargo molecules from the endolysosomal pathway and often trigger immunological reactions, limiting their effectiveness in delivering peptides, proteins, and oligonucleotides into cells.
Innovation Solution
Development of peptides derived from human and bovine lactoferrin with specific amino acid sequences, including cationic amino acids and cysteine residues, which form disulfide bonds, enabling efficient cellular uptake and rapid release of cargo molecules while minimizing immunological responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional cell-penetrating peptides are used for cargo delivery, then cellular uptake is achieved, but rapid release from the endolysosomal pathway is not achieved
Solution Approach 1:
The patent modifies the amino acid sequence parameters of conventional CPPs by incorporating specific lactoferrin-derived sequences with defined cationic residues and secondary structures, changing the biochemical parameters to achieve both efficient uptake and rapid endolysosomal release
2Productivity
If conventional cell-penetrating peptides are used for cargo delivery, then cellular uptake is achieved, but immunological reactions are triggered
Solution Approach 1:
The patent uses lactoferrin-derived peptide sequences that are copied from natural human or bovine lactoferrin proteins, leveraging the body's existing recognition of these sequences as self-proteins to reduce immunogenicity while maintaining CPP functionality
3Reliability
If peptides with high cargo binding affinity are used, then cargo complex formation is achieved, but rapid cargo release from endolysosomal pathway is hindered
Solution Approach 1:
The patent designs peptides with dynamic properties that allow stable cargo complex formation at the cell surface followed by conformational or chemical changes in the endolysosomal environment that trigger rapid cargo release, creating a time-dependent binding profile
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 lactoferrin-derived peptides effectively deliver cargo molecules into the cytoplasm, providing a means for influencing cellular mechanisms and offering therapeutic, diagnostic, and research applications with a favorable immunological profile.
Implementation Method 1
the peptide comprises at least two Cys residues or analogs thereof... the peptide comprises a disulfide bond created by two Cys residues or an analogous bond formed by the cysteine analogs
Data Source
AI summary
A peptide having an amino acid sequence containing at least eight consecutive amino acids of the human lactoferrin protein or of the bovine lactoferrin protein. The peptide is suitable as a cell-penetrating peptide. A complex of the peptide and a cargo molecule non-covalently bound to the peptide. The cargo molecule may be a nucleic acid, an amino acid, a peptide, a protein, a carbohydrate, a lipid, or a small molecule. A method of penetrating or transfecting a cell using the complex.