title: Exosome nanovesicles displaying G protein-coupled receptors for drug discovery.
abstract: Exosomes are naturally occurring nanovesicles that can be tailored to display a broad range of drug targets, including G protein-coupled receptors. Such vesicles provide a new source of complex membrane proteins that are maintained in their native conformation. Given the difficulties to isolate receptors for drug target validation and discovery, receptor presentation on exosome emerges as a promising new tool for drug screening. The potential of this technology is illustrated here with recombinant exosomes presenting the somatostatin receptor 2 as an example. The receptor-containing vesicles were identified as exosomes since they also bear Lactadherin, a hallmark of exosome nanovesicles. The amount of somatostatin receptor 2 on exosomes was similar to the amount of the most abundant known exosome membrane proteins. The receptor was functional and similar in size to the form found on cell surface. Finally, recombinant exosomes were used in several assay formats that exemplify their capacity as a new receptor presentation platform for drug discovery. These include the induction and detection of antibody as well as screening of antibody repertoires without the need to purify membrane proteins.
authors.affiliation: ExoThera LLC, Menlo Park, CA, USA.
authors.forename: Angeles
authors.initials: A
authors.lastname: Estelles
authors.forename: Jeff
authors.initials: J
authors.lastname: Sperinde
authors.forename: Thibaut
authors.initials: T
authors.lastname: Roulon
authors.forename: Barbara
authors.initials: B
authors.lastname: Aguilar
authors.forename: Caroline
authors.initials: C
authors.lastname: Bonner
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: LePecq
authors.forename: Alain
authors.initials: A
authors.lastname: Delcayre
mesh_terms: D002460:Cell Line; D015195:Drug Design; D006801:Humans; D007668:Kidney / Q000502:physiology*; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D019151:Peptide Library; D015202:Protein Engineering / Q000379:methods; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D022161:Transport Vesicles / Q000235:genetics* / Q000378:metabolism*
chemical_list: D019151:Peptide Library; D017481:Receptors, Somatostatin; D011994:Recombinant Proteins; C093733:somatostatin receptor 2