Robust In Vivo Transduction of Nervous System and Neural Stem Cells by Early Gestational Intra Amniotic Gene Transfer Using Lentiviral Vector

Presently, in vivo methods to efficiently and broadly transduce all major cell types throughout both the central (CNS) and peripheral adult nervous system (PNS) are lacking. In this study, we hypothesized that during early fetal development neural cell populations, including neural stem cells (NSCs)...

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Bibliographic Details
Published in:Molecular therapy 2010-09, Vol.18 (9), p.1615-1623
Main Authors: Stitelman, David H, Endo, Masayuki, Bora, Archana, Muvarak, Nidal, Zoltick, Philip W, Flake, Alan W, Brazelton, Timothy R
Format: Article
Language:English
Subjects:
Animals
Antibodies
Brain
Cytomegalovirus
Disease
Female
Fetuses
Genetic Vectors - genetics
Green Fluorescent Proteins - genetics
Green Fluorescent Proteins - metabolism
Immunohistochemistry
In Vitro Techniques
Lentivirus - genetics
Male
Mice
Mice, Inbred BALB C
Nervous system
Nervous System - embryology
Nervous System - metabolism
Neural Stem Cells - metabolism
Original
Proteins
Spinal cord
Stem cells
Systems development
Transduction, Genetic - methods
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Summary:Presently, in vivo methods to efficiently and broadly transduce all major cell types throughout both the central (CNS) and peripheral adult nervous system (PNS) are lacking. In this study, we hypothesized that during early fetal development neural cell populations, including neural stem cells (NSCs), may be accessible for gene transfer via the open neural groove. To test this hypothesis, we injected lentiviral vectors encoding a green fluorescent protein (GFP) marker gene into the murine amniotic cavity at embryonic day 8. This method (i) efficiently and stably transduced the entire nervous system for at least 80% of the lifespan of the mice, (ii) transduced all major neural cell types, and (iii) transduced adult NSCs of the subventricular zone (SVZ) and subgranular zones (SGZs). This simple approach has broad applications for the study of gene function in nervous system development and adult NSCs and may have future clinical applications for treatment of genetic disorders of the nervous system.
ISSN:1525-0016
1525-0024
DOI:10.1038/mt.2010.125