Adeno-associated viral vectors serotype 8 for cell-specific delivery of therapeutic genes in the central nervous system
Keywords: 
Materias Investigacion::Ciencias de la Salud
AAV
CNS
Promoters
Basal ganglia
Parkinson's disease
Gene therapy
Issue Date: 
2017
Publisher: 
Frontiers Media
ISSN: 
1662-5129
Editorial note: 
This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permission.
Note: 
CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and the source are credited.
Citation: 
Pignataro D, Sucunza D, Vanrell L, Lopez-Franco E, Dopeso-Reyes IG, Vales A, et al. Adeno-associated viral vectors serotype 8 for cell-specific delivery of therapeutic genes in the central nervous system. Front Neuroanat 2017 Feb;11:2.
Abstract
Adeno-associated viruses (AAVs) have become highly promising tools for research and clinical applications in the central nervous system (CNS). However, specific delivery of genes to the cell type of interest is essential for the success of gene therapy and therefore a correct selection of the promoter plays a very important role. Here, AAV8 vectors carrying enhanced green fluorescent protein (eGFP) as reporter gene under the transcriptional control of different CNS-specific promoters were used and compared with a strong ubiquitous promoter. Since one of the main limitations of AAV-mediated gene delivery lies in its restricted cloning capacity, we focused our work on small-sized promoters. We tested the transduction efficacy and specificity of each vector after stereotactic injection into the mouse striatum. Three glia-specific AAV vectors were generated using two truncated forms of the human promoter for glial fibrillar acidic protein (GFAP) as well as a truncated form of the murine GFAP promoter. All three vectors resulted in predominantly glial expression; however we also observed eGFP expression in other cell-types such as oligodendrocytes, but never in neurons. In addition, robust and neuron-specific eGFP expression was observed using the minimal promoters for the neural protein BM88 and the neuronal nicotinic receptor β2 (CHRNB2). In summary, we developed a set of AAV vectors designed for specific expression in cells of the CNS using minimal promoters to drive gene expression when the size of the therapeutic gene matters.

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