Engineered Extracellular Vesicle Fusion for Targeted Protein Delivery
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Solution Overview
Problem
Existing methods struggle to efficiently load non-exosomal proteins heterologously expressed in cells into extracellular vesicles for effective drug delivery, as these proteins are not spontaneously sorted into EVs.
Innovation Solution
The use of a fusion protein comprising a fusion partner, such as truncated plexins, to facilitate the enrichment of target proteins in extracellular vesicles by fusing them with the vesicle membrane, allowing for efficient loading and delivery of therapeutic peptides and proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If non-exosomal proteins are heterologously expressed in cells, then therapeutic proteins can be produced, but these proteins are not spontaneously sorted into extracellular vesicles for effective delivery
Solution Approach 1:
The patent introduces an intermediary protein (such as CD63, CD81, or TSG101) that acts as a mediator between the heterologously expressed therapeutic protein and the extracellular vesicle membrane. This intermediary protein is fused with the therapeutic protein and serves as a recognition signal for EV incorporation, enabling reliable sorting and enrichment of the therapeutic protein into EVs without requiring spontaneous sorting.
2Productivity
If traditional methods are used to load proteins into EVs, then some protein loading is achieved, but the efficiency and reliability are insufficient for effective drug delivery
Solution Approach 1:
The patent applies preliminary action by fusing the intermediary protein with the therapeutic protein before cell expression. This pre-fusion ensures that when the therapeutic protein is produced, it is already equipped with the necessary sorting signals to be efficiently incorporated into EVs. The intermediary protein is strategically positioned to recognize EV membrane components in advance, guaranteeing reliable enrichment during the EV formation process.
Data Source
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AI summary
The present invention provides an engineered extracellular vesicle, a pharmaceutical composition containing the engineered extracellular vesicle and a use thereof, and further provides a method for constructing the engineered extracellular vesicle. The engineered extracellular vesicle can be used for drug delivery, enrichment of target proteins in extracellular vesicles, or display of target proteins.