Engineered Extracellular Vesicles for Target Protein Loading
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Solution Overview
Problem
Existing methods struggle to efficiently load non-exosomal proteins heterologously expressed in cells into extracellular vesicles, limiting the effectiveness of target proteins carried by EVs for therapeutic purposes.
Innovation Solution
The use of a fusion protein comprising a fusion partner, such as truncated plexins, to facilitate the enrichment of target proteins on extracellular vesicles by fusing a transmembrane protein with a target protein, allowing for efficient loading and delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If non-exosomal proteins are heterologously expressed in cells, then the target protein can be produced, but the protein is not spontaneously sorted into extracellular vesicles
Solution Approach 1:
The patent introduces a fusion partner protein as an intermediary that mediates between the target protein and the extracellular vesicle membrane. This fusion partner contains a transmembrane domain that inserts into the EV membrane and an extracellular domain that binds the target protein, thereby facilitating the sorting and enrichment of target proteins into EVs without requiring spontaneous sorting.
Solution Approach 2:
The patent segments the protein loading function into two distinct components: the fusion partner that interacts with the EV membrane and the target protein that carries the therapeutic payload. This segmentation allows independent optimization of each component's function and enables controlled assembly of the protein complex onto the EV surface.
2Reliability
If existing protein loading methods are used, then some target proteins can be loaded into EVs, but the loading efficiency is insufficient for therapeutic effectiveness
Solution Approach 1:
The patent employs preliminary action by pre-fusing the target protein to the fusion partner protein before the EV formation process. This pre-assembly ensures that the target protein is already positioned on the EV surface when the vesicle is formed, significantly improving loading efficiency and ensuring sufficient protein amounts for therapeutic effectiveness.
Data Source
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.