BBB-targeting, protein-based nanomedicines for drug and nucleic acid delivery to the CNS

Hugo Peluffo, Ugutz Unzueta, María Luciana Negro-Demontel, Zhikun Xu, Esther Váquez, Neus Ferrer-Miralles, Antonio Villaverde

Research output: Contribution to journalReview articleResearchpeer-review

67 Citations (Scopus)


© 2015 Elsevier Inc. 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.
Original languageEnglish
Pages (from-to)277-287
JournalBiotechnology Advances
Issue number2
Publication statusPublished - 1 Jan 2015


  • Artificial viruses
  • BBB
  • Drug delivery
  • Gene therapy
  • Nanoparticles
  • Protein engineering
  • Recombinant proteins


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