Engineering intercellular communication has long been a goal of Synthetic Biologists, and while its been met with success in model organisms like S. cerevisiae and E. coli, such tools are unavailable for use in mammalian cell types. Exosomes, one way mammalian cells communicate, are 30-100 nanometer extracellular vesicles of endosomal origin that contain a myriad of biologically active molecules. From proteomic analysis and RNA sequencing, we know that the contents of exosomes are distinct from those of other cell types and even distinct from its cell of origin. This implies an active targeting process involved in packaging biomolecules into exosomes. Here, we tether proteins of interest to common exosomal marker proteins like CD63 as a mechanism for targeting proteins into exosomes.

We know so little about exosomes, and that presents a huge engineering challenge. How do we engineer that which we dont understand? It leads to fun trial-and-error experimentation that provides a great exercise for the imagination.