title: Barriers to non-viral vector-mediated gene delivery in the nervous system.
abstract: Efficient methods for cell line transfection are well described, but, for primary neurons, a high-yield method different from those relying on viral vectors is lacking. Viral transfection has several drawbacks, such as the complexity of vector preparation, safety concerns, and the generation of immune and inflammatory responses when used in vivo. However, one of the main problems for the use of non-viral gene vectors for neuronal transfection is their low efficiency when compared with viral vectors. Transgene expression, or siRNA delivery mediated by non-viral vectors, is the result of multiple processes related to cellular membrane crossing, intracellular traffic, and/or nuclear delivery of the genetic material cargo. This review will deal with the barriers that different nanoparticles (cationic lipids, polyethyleneimine, dendrimers and carbon nanotubes) must overcome to efficiently deliver their cargo to central nervous system cells, including internalization into the neurons, interaction with intracellular organelles such as lysosomes, and transport across the nuclear membrane of the neuron in the case of DNA transfection. Furthermore, when used in vivo, the nanoparticles should efficiently cross the blood-brain barrier to reach the target cells in the brain.
authors.affiliation: NanoDrugs, S.L. Parque Científico y Tecnológico, Albacete, Spain.
authors.forename: Francisco C
authors.initials: FC
authors.lastname: Pérez-Martínez
authors.forename: Javier
authors.initials: J
authors.lastname: Guerra
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Posadas
authors.forename: Valentín
authors.initials: V
authors.lastname: Ceña
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage*; D014162:Transfection