Lentiviral vectors as tools to understand central nervous system biology in mammalian model organisms

Lentiviruses have been extensively used as gene delivery vectors since the mid-1990’s. Usually derived from the human immunodeficiency virus (HIV) genome, they mediate efficient gene transfer to non-dividing cells, including neurons and glia in the adult mammalian brain. In addition, integration of...

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Main Authors: Stephanie Margaret Hughes, Louise C. Parr-Brownlie, Clementine eBosch-Bouju, Lucia eSchoderboeck, Rachel eSizemore, Wickliffe eAbraham
Format: Article
Language:English
Published: Frontiers Media S.A. 2015-05-01
Series:Frontiers in Molecular Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fnmol.2015.00014/full
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author Stephanie Margaret Hughes
Louise C. Parr-Brownlie
Clementine eBosch-Bouju
Lucia eSchoderboeck
Rachel eSizemore
Wickliffe eAbraham
author_facet Stephanie Margaret Hughes
Louise C. Parr-Brownlie
Clementine eBosch-Bouju
Lucia eSchoderboeck
Rachel eSizemore
Wickliffe eAbraham
author_sort Stephanie Margaret Hughes
collection DOAJ
description Lentiviruses have been extensively used as gene delivery vectors since the mid-1990’s. Usually derived from the human immunodeficiency virus (HIV) genome, they mediate efficient gene transfer to non-dividing cells, including neurons and glia in the adult mammalian brain. In addition, integration of the recombinant lentiviral construct into the host genome provides permanent expression, including the progeny of dividing neural precursors. In this review, we describe targeted vectors with modified envelope glycoproteins and expression of transgenes under the regulation of cell-selective and inducible promoters. This technology has broad utility to address fundamental questions in neuroscience and we outline how this has been used in rodents and primates. Combining viral tract tracing with immunohistochemistry and confocal or electron microscopy, lentiviral vectors provide a tool to selectively label and trace specific neuronal populations at gross or ultrastructural levels. Additionally, new generation optogenetic technologies can be readily utilized to analyse neuronal circuit and gene functions in the mature mammalian brain. Examples of these applications, limitations of current systems and prospects for future developments to enhance neuroscience knowledge will be reviewed. Finally, we will discuss how these vectors may be translated from gene therapy trials into the clinical setting.
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spelling doaj.art-edafda692f5c4e49b9db60d3a7f9d4952022-12-21T23:57:08ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992015-05-01810.3389/fnmol.2015.00014139563Lentiviral vectors as tools to understand central nervous system biology in mammalian model organismsStephanie Margaret Hughes0Louise C. Parr-Brownlie1Clementine eBosch-Bouju2Lucia eSchoderboeck3Rachel eSizemore4Wickliffe eAbraham5University of OtagoUniversity of OtagoUniversity of BordeauxUniversity of OtagoUniversity of OtagoUniversity of OtagoLentiviruses have been extensively used as gene delivery vectors since the mid-1990’s. Usually derived from the human immunodeficiency virus (HIV) genome, they mediate efficient gene transfer to non-dividing cells, including neurons and glia in the adult mammalian brain. In addition, integration of the recombinant lentiviral construct into the host genome provides permanent expression, including the progeny of dividing neural precursors. In this review, we describe targeted vectors with modified envelope glycoproteins and expression of transgenes under the regulation of cell-selective and inducible promoters. This technology has broad utility to address fundamental questions in neuroscience and we outline how this has been used in rodents and primates. Combining viral tract tracing with immunohistochemistry and confocal or electron microscopy, lentiviral vectors provide a tool to selectively label and trace specific neuronal populations at gross or ultrastructural levels. Additionally, new generation optogenetic technologies can be readily utilized to analyse neuronal circuit and gene functions in the mature mammalian brain. Examples of these applications, limitations of current systems and prospects for future developments to enhance neuroscience knowledge will be reviewed. Finally, we will discuss how these vectors may be translated from gene therapy trials into the clinical setting.http://journal.frontiersin.org/Journal/10.3389/fnmol.2015.00014/fullLentivirusoptogeneticsconfocal and electron microscopy)temporal and spatial specificityneuron phenotype
spellingShingle Stephanie Margaret Hughes
Louise C. Parr-Brownlie
Clementine eBosch-Bouju
Lucia eSchoderboeck
Rachel eSizemore
Wickliffe eAbraham
Lentiviral vectors as tools to understand central nervous system biology in mammalian model organisms
Frontiers in Molecular Neuroscience
Lentivirus
optogenetics
confocal and electron microscopy)
temporal and spatial specificity
neuron phenotype
title Lentiviral vectors as tools to understand central nervous system biology in mammalian model organisms
title_full Lentiviral vectors as tools to understand central nervous system biology in mammalian model organisms
title_fullStr Lentiviral vectors as tools to understand central nervous system biology in mammalian model organisms
title_full_unstemmed Lentiviral vectors as tools to understand central nervous system biology in mammalian model organisms
title_short Lentiviral vectors as tools to understand central nervous system biology in mammalian model organisms
title_sort lentiviral vectors as tools to understand central nervous system biology in mammalian model organisms
topic Lentivirus
optogenetics
confocal and electron microscopy)
temporal and spatial specificity
neuron phenotype
url http://journal.frontiersin.org/Journal/10.3389/fnmol.2015.00014/full
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