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Updated: Jan 9, 2026
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Engineering Cell-permeable Protein
Published on: December 28, 2009
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Efficient cellular transformation via protein delivery through the protrusion-derived extracellular vesicles
Toshifumi Fujioka1, Tamako Nishimura2, Hiroki Kawana1
1Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Japan.
Nature Communications
|December 8, 2025
Summary
Protrusion-derived extracellular vesicles (EVs) efficiently deliver functional proteins like Rac1 and Cas12f. These EVs offer a superior platform for bioactive protein transfer compared to endosome-derived EVs.
Area of Science:
- Cell biology
- Biotechnology
- Molecular medicine
Background:
- Extracellular vesicles (EVs) facilitate intercellular protein transfer.
- EVs originate from either plasma membrane protrusions or endosomes.
- The efficiency and functionality of protein delivery via different EV types are not well understood.
Purpose of the Study:
- To compare the protein transfer efficiency and functionality of protrusion-derived EVs versus endosome-derived EVs.
- To investigate the mechanism of cargo delivery by protrusion-derived EVs.
- To explore the potential of protrusion-derived EVs for delivering engineered proteins.
Main Methods:
- Utilized MIM protein to isolate protrusion-derived EVs.
- Engineered EVs to package genome-editing protein Cas12f.
- Quantified protein delivery via endocytosis and cytosolic release.
- Assessed functional outcomes, such as enhanced cell motility.
Main Results:
- Protrusion-derived EVs, dependent on MIM, deliver functional small GTPase Rac1 protein effectively.
- Rac1-containing EVs are internalized, trafficked through endosomes, and released into the cytosol, enhancing cell motility.
- Protrusion-derived EVs exhibit significantly higher efficiency in delivering the genome-editing protein Cas12f compared to endosome-derived EVs.
Conclusions:
- Protrusion-derived EVs are a highly efficient platform for delivering native and engineered proteins.
- These EVs demonstrate superior capability for functional protein transfer.
- Findings expand EV-based therapeutic strategies for bioactive protein delivery.
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