Engineering yeast extracellular vesicles for therapeutic delivery

Extracellular vesicles, often called EVs or exosomes, are tiny membrane-bound particles released by cells that can carry proteins, RNA, and other molecules. Because of this, they are gaining attention as potential delivery systems for therapeutics. Researchers at Tianjin University explored how to better understand and engineer EV production using yeast.

The team focused on Saccharomyces cerevisiae, a well-known and widely used laboratory organism. Yeast is considered a safe and highly controllable system, making it an attractive platform for studying how EVs are formed and how they can be engineered to carry useful cargo.

To test this, the researchers introduced a therapeutic protein, chicken interferon lambda, into yeast cells. They also applied mild stress to the yeast cell wall. Together, these changes led to a dramatic increase in EV production, about ten times higher than normal, and improved the loading of the therapeutic protein into the vesicles.

To better understand what was happening inside the cells, the team used proteomics to analyze the proteins present in the EVs. They identified more than 1,500 proteins, including many that are normally involved in transporting materials within the cell. Interestingly, when the yeast was engineered to produce more EVs, key trafficking systems such as SNARE, ESCRT, and Rab proteins were altered. This suggests that the cells were actively rewiring how materials move internally to support EV production.

Further experiments showed that specific SNARE proteins, including Sso2 and Nyv1, play an important role in shaping EV size and composition. This highlights that EV formation is not random but controlled by specific molecular machinery.

Overall, the findings demonstrate that yeast can be engineered to produce extracellular vesicles more efficiently and to package therapeutic proteins inside them. This opens the door to scalable, cost-effective production of EV-based therapeutics using a microbial system. It also provides new insight into the biological processes that control vesicle formation, which could be applied across different organisms and therapeutic applications.

Li Y, Ma X, Zhang L, Cao N, Li Z, Khoo R, Wang M, Li C, Hua D, Zheng X, Huang J, Zhang L. (2026) Engineering Yeast Extracellular Vesicle Biogenesis Through Rewiring Membrane Trafficking Pathways. Microbial Biotechnology 19(4): e70338. [article]

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