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), 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.
Stitelman
David H
DH
The Children's Center for Fetal Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Endo
Masayuki
M
Bora
Archana
A
Muvarak
Nidal
N
Zoltick
Philip W
PW
Flake
Alan W
AW
Brazelton
Timothy R
TR
D000818:Animals; D005260:Female; D005822:Genetic Vectors / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009420:Nervous System / Q000196:embryology / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D014161:Transduction, Genetic / Q000379:methods*
D049452:Green Fluorescent Proteins