title: BBB-targeting, protein-based nanomedicines for drug and nucleic acid delivery to the CNS.
abstract: The increasing incidence of diseases affecting the central nervous system (CNS) demands the urgent development of efficient drugs. While many of these medicines are already available, the Blood Brain Barrier and to a lesser extent, the Blood Spinal Cord Barrier pose physical and biological limitations to their diffusion to reach target tissues. Therefore, efforts are needed not only to address drug development but specially to design suitable vehicles for delivery into the CNS through systemic administration. In the context of the functional and structural versatility of proteins, recent advances in their biological fabrication and a better comprehension of the physiology of the CNS offer a plethora of opportunities for the construction and tailoring of plain nanoconjugates and of more complex nanosized vehicles able to cross these barriers. We revise here how the engineering of functional proteins offers drug delivery tools for specific CNS diseases and more transversally, how proteins can be engineered into smart nanoparticles or 'artificial viruses' to afford therapeutic requirements through alternative administration routes.
authors.affiliation: Neuroinflammation Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay; Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República (UDELAR), Montevideo, Uruguay.
authors.forename: Hugo
authors.initials: H
authors.lastname: Peluffo
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; Department de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, 08193 Barcelona, Spain.
authors.forename: Ugutz
authors.initials: U
authors.lastname: Unzueta
authors.affiliation: Neuroinflammation Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay; Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República (UDELAR), Montevideo, Uruguay.
authors.forename: María Luciana
authors.initials: ML
authors.lastname: Negro-Demontel
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; Department de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, 08193 Barcelona, Spain.
authors.forename: Zhikun
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; Department de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, 08193 Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Váquez
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; Department de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, 08193 Barcelona, Spain.
authors.forename: Neus
authors.initials: N
authors.lastname: Ferrer-Miralles
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; Department de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, 08193 Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Villaverde
mesh_terms: D001812:Blood-Brain Barrier / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects* / Q000473:pathology; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000473:pathology; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D006801:Humans; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D009696:Nucleic Acids / Q000627:therapeutic use
chemical_list: D009696:Nucleic Acids
keywords: Artificial viruses; BBB; Drug delivery; Gene therapy; Nanoparticles; Protein engineering; Recombinant proteins