AAV2 vectors mediate efficient and sustained transduction of rat embryonic ventral mesencephalon.
The success of transplantation of human embryonic mesencephalic tissue to treat parkinsonian patients is limited by the poor survival of the transplant. We show that an AAV2 vector mediates efficient expression of the egfp reporter gene in organotypic cultures of freshly explanted solid fragments of rat embryonic ventral mesencephalon (VM). We observed early and sustained transgene expression (4 days to > or = 6 weeks). Furthermore, rAAV-infected rat embryonic VM transplanted in the adult striatum continued to express EGFP for > or = 3 months. More than 95% of the transduced cells were neurons. Dopaminergic neurons were transduced at low frequency at earlier time points. This method of gene delivery could prove useful to achieve local, continuous secretion of neurotrophic factors at physiologically relevant doses to treat Parkinson's disease.
Lehtonen
E
E
Laboratory of Experimental Neurosurgery, ULB, Belgium.
Bonnaud
F
F
Melas
C
C
Lubansu
A
A
Malgrange
B
B
Chtarto
A
A
Velu
T
T
Brotchi
J
J
Levivier
M
M
Peschanski
M
M
Tenenbaum
L
L
D000818:Animals; D016380:Brain Tissue Transplantation; D004298:Dopamine / Q000502:physiology; D016332:Fetal Tissue Transplantation; D015870:Gene Expression / Q000502:physiology; D005822:Genetic Vectors; D006085:Graft Survival / Q000502:physiology; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D008636:Mesencephalon / Q000637:transplantation; D009410:Nerve Degeneration / Q000503:physiopathology; D009924:Organ Culture Techniques; D020734:Parkinsonian Disorders / Q000601:surgery*; D051381:Rats; D017208:Rats, Wistar
D007202:Indicators and Reagents; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D004298:Dopamine