Lentiviral vectors as tools to understand central nervous system biology in mammalian model organisms
Front. Mol. Neurosci.. 2015-05-18; 8:
DOI: 10.3389/fnmol.2015.00014
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1. Front Mol Neurosci. 2015 May 18;8:14. doi: 10.3389/fnmol.2015.00014. eCollection
2015.
Lentiviral vectors as tools to understand central nervous system biology in
mammalian model organisms.
Parr-Brownlie LC(1), Bosch-Bouju C(2), Schoderboeck L(3), Sizemore RJ(1), Abraham
WC(4), Hughes SM(5).
Author information:
(1)Department of Anatomy, Brain Health Research Centre, University of Otago
Dunedin, New Zealand ; Brain Research New Zealand Centre of Research Excellence
Dunedin, New Zealand.
(2)NutriNeuro, UMR 1286 INRA, University of Bordeaux Bordeaux, France.
(3)Brain Research New Zealand Centre of Research Excellence Dunedin, New Zealand
; Department of Biochemistry, Brain Health Research Centre, University of Otago
Dunedin, New Zealand ; Department of Psychology, Brain Health Research Centre,
University of Otago Dunedin, New Zealand.
(4)Brain Research New Zealand Centre of Research Excellence Dunedin, New Zealand
; Department of Psychology, Brain Health Research Centre, University of Otago
Dunedin, New Zealand.
(5)Brain Research New Zealand Centre of Research Excellence Dunedin, New Zealand
; Department of Biochemistry, Brain Health Research Centre, University of Otago
Dunedin, New Zealand.
Lentiviruses have been extensively used as gene delivery vectors since the
mid-1990s. Usually derived from the human immunodeficiency virus 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 analyze 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.
DOI: 10.3389/fnmol.2015.00014
PMCID: PMC4434958
PMID: 26041987