Unique sEV bioengineering technology
Any type of protein, even the most complex ones, can be targeted to the sEV lumen or surface.
Ciloa has developed a unique patented technology of sEV bioengineering based on a Pilot Peptide (PP) that interacts with the ESCRT cellular machinery responsible sEV production.
All types of proteins, even the most complex, can be sorted into the small extracellular vesicle (sEV) lumen or onto the sEV surface, where they are anchored in the membrane.
In short, a chimeric DNA that encodes the protein of interest fused to the Pilot Peptide sequence is constructed and introduced into cells. The cells synthesize the protein, operating quality control mechanisms that include natural post-translational modifications. Then, the PP targets the fully native, mature protein to the ESCRT machinery and finally, the sEVs containing the desired protein are secreted out of the cells.
It should be noted that, in terms of the challenge of sorting fully native membrane proteins out of cells, Ciloa technology successfully benefits from several natural cellular pathways.
- The ER/Golgi pathway allows for the synthesis, correct folding, oligomerization, and post-translational modifications of membrane proteins. At each step, the membrane proteins are submitted to strong quality controls.
- The combination of a previously undescribed process that selects only mature proteins and a specific sorting pathway involving ESCRT machinery that allows the secretion outside of cells of fully native and functional membrane proteins embedded in the membrane of sEVs is unprecedented.
Bioengineering capabilities
Ciloa has developed the sole technology to produce all types of complex membrane proteins on sEVs. This allows to work with the families of membrane proteins that are called “undruggable”, but that are also the most promising therapeutic targets.
Summary
Aspect |
Details |
Mechanism |
Fuses proteins with pilot peptide, uses ER/Golgi and ESCRT pathways |
Production Achievements |
Over 130 proteins, including 60 membrane proteins (GPCRs, Ion channels, Viral envelope proteins, Kinase receptors, Ig Superfamily, etc.) |
Applications |
Therapeutic sEVs, vaccines, drug delivery, antibodies, immunotherapies |
Disease Areas |
Metabolic diseases, oncology, infectious diseases |
Patent Status |
International granted patents, exclusive licenses |
Recognition |
Sanofi iTech Awards, FUI, Eurostars, France 2030 |