Lentiviral vectors mediate efficient and stable gene transfer in adult neural stem cells in vivo.
Modulation of adult neurogenesis may offer new therapeutic strategies for various brain disorders. In the adult mammalian brain the subventricular zone (SVZ) of the lateral ventricle is a region of continuous neurogenesis. Lentiviral vectors stably integrate into dividing and nondividing cells, in contrast to retroviral vectors, which integrate only into dividing cells. We compared their potential for gene transfer into both quiescent and slowly dividing stem cells as well as into more rapidly dividing progenitor cells. In contrast to retroviral vectors, stereotactic injection of lentiviral vectors into the SVZ of adult mice resulted in efficient and long-term marker gene expression in cells with characteristics of both immature type B cells and migrating precursor cells. After migration along the rostral migratory stream and differentiation, the number of enhanced green fluorescent protein (eGFP)-expressing granular and periglomerular interneurons increased over time in the ipsilateral olfactory bulb. Moreover, the number of eGFP-labeled neuronal progenitor cells in the SVZ increased over time. By intraventricular injection of lentiviral vectors we could restrict gene transfer to ependymal cells and type B astroglial-like stem cells. In conclusion, lentiviral vectors surpass retroviral vectors in efficient long-term in vivo marking of subventricular zone stem cells for basic research and therapeutic applications.
Geraerts
Martine
M
Laboratory for Molecular Virology and Gene Therapy, Katholieke Universiteit Leuven and IRC KULAK (Interdisciplinary Research Center, Katholieke Universiteit Leuven-Campus Kortrijk), Leuven, 3000, Belgium.
Eggermont
Kristel
K
Hernandez-Acosta
Pilar
P
Garcia-Verdugo
Jose-Manuel
JM
Baekelandt
Veerle
V
Debyser
Zeger
Z
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000821:virology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004805:Ependyma / Q000166:cytology / Q000821:virology; D005260:Female; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007276:Injections, Intraventricular; D007395:Interneurons / Q000166:cytology / Q000502:physiology*; D020547:Lateral Ventricles / Q000166:cytology / Q000821:virology; D016086:Lentivirus / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism; D011994:Recombinant Proteins / Q000032:analysis; D013234:Stem Cells / Q000166:cytology / Q000502:physiology* / Q000821:virology; D013997:Time Factors; D014162:Transfection / Q000379:methods
D011994:Recombinant Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins