Polypeptide EXP for Exosome Surface Functionalization
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Solution Overview
Problem
Current methods for surface functionalization of extracellular vesicles, such as exosomes, face limitations in binding efficiency and recovery efficiency, hindering their application as drug delivery vectors due to low transfection efficiency and unclear conformation of targeting peptide fusion expression.
Innovation Solution
A new polypeptide named EXP with a higher binding efficiency to exosomes, particularly those in serum, is developed, allowing for enhanced surface functionalization and extraction of extracellular vesicles by binding to CD63 and/or CD81 proteins, and can be covalently conjugated with pharmacodynamically active molecules for targeted drug delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If recombinant plasmids are used to fuse targeting peptide with membrane protein source cells to achieve surface modification of exosomes, then surface functionalization is achieved, but transfection efficiency is low and recovery efficiency is low
Solution Approach 1:
The invention extracts the essential binding function from the complex recombinant plasmid system and isolates it into a standalone targeting peptide (EXP) that directly binds to exosome surface proteins CD63 and/or CD81. This extraction eliminates the need for plasmid transfection while retaining the surface functionalization capability, thereby resolving the contradiction between ease of manufacture and productivity.
Solution Approach 2:
The invention introduces an intermediary targeting peptide (EXP) that mediates the binding between the drug delivery system and exosomes. This peptide acts as a bridge that enables surface functionalization without requiring cellular transfection processes, thus improving both transfection efficiency and recovery efficiency while maintaining the surface modification capability.
2Ease of manufacture
If CP05 polypeptide is used for exosome binding, then surface modification is achieved, but binding efficiency is limited especially to exosomes with low CD63 expression
Solution Approach 1:
The invention changes the binding parameters by designing a new peptide sequence (EXP) with optimized amino acid composition that enhances affinity for CD63 and CD81 proteins. This parameter change in the peptide structure results in significantly improved binding efficiency across all exosome types, including those with low CD63 expression, while maintaining the surface modification capability.
Solution Approach 2:
The invention creates a composite binding mechanism by incorporating multiple binding motifs within the EXP peptide that can interact with different exosome surface proteins (CD63 and/or CD81). This composite approach ensures reliable binding even when one target protein is present at low levels, thereby improving reliability while preserving surface modification functionality.
3Reliability
If exosomes are used as drug delivery vectors, then high histocompatibility and low immunogenicity are achieved, but loading efficiency is limited
Solution Approach 1:
The invention applies preliminary action by pre-conjugating the targeting peptide (EXP) with pharmacodynamically active molecules or drug delivery vectors before introducing them to exosomes. This pre-preparation ensures high loading efficiency from the outset while maintaining the natural histocompatibility and low immunogenicity of exosomes, as the modification occurs outside the cellular system.
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
EXP significantly improves the binding and extraction efficiency of exosomes, leading to a more stable and efficient drug delivery system, overcoming previous limitations in transfection efficiency and enabling improved clinical application of extracellular vesicles.
Implementation Method 1
A new polypeptide named EXP with a higher binding efficiency to exosomes, particularly those in serum, is developed, allowing for enhanced surface functionalization and extraction of extracellular vesicles by binding to CD63 and/or CD81 proteins
Data Source
AI summary
The present invention “A polypeptide EXP and its drug delivery system as well as extracellular vesicle extraction kit thereof” belongs to the field of biomedical engineering and diagnostics. The amino acid sequence of the polypeptide EXP is set forth in SEQ ID NO. 1. Based on the polypeptide EXP, the present invention also provides a drug delivery system, targeted drug delivery system, enhanced drug delivery vehicle, a drug with enhanced delivery, targeted drug, extracellular vesicle extraction kit, disease diagnostic kit, a method for purifying extracellular vesicles, and use of the polypeptide EXP in pharmacy and diagnostic reagent manufacture.