title: Delivery of Therapeutic Proteins via Extracellular Vesicles: Review and Potential Treatments for Parkinson's Disease, Glioma, and Schwannoma.
abstract: Extracellular vesicles present an attractive delivery vehicle for therapeutic proteins. They intrinsically contain many proteins which can provide information to other cells. Advantages include reduced immune reactivity, especially if derived from the same host, stability in biologic fluids, and ability to target uptake. Those from mesenchymal stem cells appear to be intrinsically therapeutic, while those from cancer cells promote tumor progression. Therapeutic proteins can be loaded into vesicles by overexpression in the donor cell, with oligomerization and membrane sequences increasing their loading. Examples of protein delivery for therapeutic benefit in pre-clinical models include delivery of: catalase for Parkinson's disease to reduce oxidative stress and thus help neurons to survive; prodrug activating enzymes which can convert a prodrug which crosses the blood-brain barrier into a toxic chemotherapeutic drug for schwannomas and gliomas; and the apoptosis-inducing enzyme, caspase-1 under a Schwann cell specific promoter for schwannoma. This therapeutic delivery strategy is novel and being explored for a number of diseases.
authors.affiliation: Departments of Chemistry and Chemical Biology and Molecular Medicine, Cornell University, Ithaca, NY, 14853, USA.|Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA, 02114, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Hall
authors.affiliation: Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA, 02114, USA.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Prabhakar
authors.affiliation: Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA, 02114, USA.
authors.forename: Leonora
authors.initials: L
authors.lastname: Balaj
authors.affiliation: Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA, 02114, USA.|Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan.
authors.forename: Charles P
authors.initials: CP
authors.lastname: Lai
authors.affiliation: Departments of Chemistry and Chemical Biology and Molecular Medicine, Cornell University, Ithaca, NY, 14853, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Cerione
authors.affiliation: Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA, 02114, USA. breakefield@hms.harvard.edu.|Molecular Neurogenetics Unit, Massachusetts General Hospital-East, 13th Street, Building 149, Charlestown, MA, 02129, USA. breakefield@hms.harvard.edu.
authors.forename: Xandra O
authors.initials: XO
authors.lastname: Breakefield
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016503:Drug Delivery Systems; D000067128:Extracellular Vesicles / Q000378:metabolism*; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009442:Neurilemmoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins
keywords: Exosomes; Extracellular vesicles; Glioma; Parkinson’s disease; Schwannoma; Therapeutic protein delivery