https://www.nature.com/articles/s41467-025-66351-1

https://www.jst.go.jp/pr/announce/20251208/index.html

A Japanese team has demonstrate that natural extracellular vehicles EVs derived from cell protrusions dependent on the I-BAR protein MIM, rather than from endosomes, deliver the functional small GTPase Rac1 protein at levels similar to microinjection. Rac1-containing EVs are internalized via endocytosis, trafficked through endosomal compartments, and subsequently released into the cytosol, where they enhance cell motility.

To evaluate broader applicability, the genome-editing protein Cas12f was packaged into protrusion-derived EVs by a protein MIM and endosome-derived EVs by endosomal tetraspanin CD63. Notably, protrusion-derived EVs delivered Cas12f with significantly higher efficiency than endosome-derived EVs, highlighting their superior capability for functional protein transfer.

These findings establish the protrusion-derived EVs as a powerful platform for the efficient and bioactive delivery of both native and engineered proteins, expanding the EV-based therapeutic strategies.