Comparative analysis of lentiviral vectors and modular protein nanovectors for traumatic brain injury gene therapy
Negro-Demontel, María Luciana (Universidad de la República (Uruguay). Departamento de Histología y Embriología)
Saccardo, Paolo (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Giacomini, Cecilia (Universidad de la República (Uruguay). Departamento de Biociencias)
Yáñez-Muñoz, Rafael (University of London. Royal Holloway)
Ferrer-Miralles, Neus (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Vázquez Gómez, Esther (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Villaverde Corrales, Antonio (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)

Date:	2014
Abstract:	Traumatic brain injury (TBI) remains as one of the leading causes of mortality and morbidity worldwide and there are no effective treatments currently available. Gene therapy applications have emerged as important alternatives for the treatment of diverse nervous system injuries. New strategies are evolving with the notion that each particular pathological condition may require a specific vector. Moreover, the lack of detailed comparative studies between different vectors under similar conditions hampers the selection of an ideal vector for a given pathological condition. The potential use of lentiviral vectors versus several modular protein-based nanovectors was compared using a controlled cortical impact model of TBI under the same gene therapy conditions. We show that variables such as protein/DNA ratio, incubation volume, and presence of serum or chloroquine in the transfection medium impact on both nanovector formation and transfection efficiency in vitro. While lentiviral vectors showed GFP protein 1 day after TBI and increased expression at 14 days, nanovectors showed stable and lower GFP transgene expression from 1 to 14 days. No toxicity after TBI by any of the vectors was observed as determined by resulting levels of IL-1β or using neurological sticky tape test. In fact, both vector types induced functional improvement per se.
Grants:	Ministerio de Ciencia e Innovación ACI2009-0919 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-108
Note:	Altres ajuts: We thank Fundació Marató TV3 (110533), Catalunya, Spain, Comisión Sectorial de Investigación Científica (CSIC-UDELAR), Uruguay, Agencia Nacional de Investigación e Innovación (ANII), Uruguay, PEDECIBA, Uruguay, FOCEM (MERCOSUR Structural Convergence Fund), COF 03/1111 (to H.P. and M.L.N.), and Genoma España (Project GENAME, to R.J.Y.-M.) for financial support. A.V. received support from Centro de Investigación Biomédica en Red (CIBER) de Bioingeniería, Biomateriales y Nanomedicina, with assistance from the European Regional Development Fund. A.V. has been distinguished with an ICREA ACADEMIA award.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials i que es distribueixin sota la mateixa llicència que regula l'obra original. Cal que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Regeneration ; Repair ; Nervous system ; Regeneració ; Reparació ; Sistema nerviós
Published in:	Molecular Therapy. Methods & Clinical Development, 2014, article 14047, ISSN 2329-0501

DOI: 10.1038/mtm.2014.47
PMID: 26015985

11 p, 1019.7 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
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