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Mol Ther Methods Clin Dev. 2014 Oct 15;1:14047. doi: 10.1038/mtm.2014.47. eCollection 2014.

Comparative analysis of lentiviral vectors and modular protein nanovectors for traumatic brain injury gene therapy.

Author information

1
Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo , Montevideo, Uruguay ; Departmento de Histología y Embriología, Facultad de Medicina, UDELAR , Montevideo, Uruguay.
2
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona , Barcelona, Spain ; Department de Genètica i de Microbiologia, Universitat Autònoma de Barcelona , Barcelona, Spain ; CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) , Barcelona, Spain.
3
Cátedra de Bioquímica, Departamento de Biociencias, Facultad de Química, UDELAR , Montevideo, Uruguay.
4
Royal Holloway University of London , Egham, UK.

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.

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