caa a22 4500 445313641 CHVBK 20180317142638.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s11095-010-0364-7 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0364-7 Barriers to Non-Viral Vector-Mediated Gene Delivery in the Nervous System [Elektronische Daten] [Francisco Pérez-Martínez, Javier Guerra, Inmaculada Posadas, Valentín Ceña] 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. The Author(s), 2011 delivery nationallicence gene therapy nationallicence membrane crossing nationallicence nanoparticles nationallicence neurons nationallicence Pérez-Martínez Francisco NanoDrugs, S.L. Parque Científico y Tecnológico, Albacete, Spain aut Guerra Javier Departamento de Química Inorgánica, Orgánica y Bioquímica Facultad de Química-IRICA, Universidad de Castilla-La Mancha, Ciudad Real, Spain aut Posadas Inmaculada Unidad Asociada Neurodeath, Departamento de Ciencias Médicas, CSIC-Universidad de Castilla-La Mancha, Albacete, Spain aut Ceña Valentín Unidad Asociada Neurodeath, Departamento de Ciencias Médicas, CSIC-Universidad de Castilla-La Mancha, Albacete, Spain aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 1843-1858 0724-8741 28:8<1843 2011 28 11095 https://doi.org/10.1007/s11095-010-0364-7 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0364-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pérez-Martínez Francisco NanoDrugs, S.L. Parque Científico y Tecnológico, Albacete, Spain aut NATIONALLICENCE 700 1- Guerra Javier Departamento de Química Inorgánica, Orgánica y Bioquímica Facultad de Química-IRICA, Universidad de Castilla-La Mancha, Ciudad Real, Spain aut NATIONALLICENCE 700 1- Posadas Inmaculada Unidad Asociada Neurodeath, Departamento de Ciencias Médicas, CSIC-Universidad de Castilla-La Mancha, Albacete, Spain aut NATIONALLICENCE 700 1- Ceña Valentín Unidad Asociada Neurodeath, Departamento de Ciencias Médicas, CSIC-Universidad de Castilla-La Mancha, Albacete, Spain aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 1843-1858 0724-8741 28:8<1843 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer