Readministration of adenoviral gene delivery to dopamine neurons.
An approach currently being explored as treatment for Parkinson's disease is gene therapy. An important question concerns the duration of transgene expression in dopamine neurons and the issues of vector persistence, neuronal damage and the feasibility of readministering vector to the same neuronal population. We show, using an adenoviral vector expressing the LacZ reporter gene, that transgene expression declined over time but with minimal loss of dopamine neurons or vector DNA. Readministration of vector resulted in low levels of transgene delivery to the neurons. Moreover, the neurons to which vector had already been delivered were unable to transport the retrograde tracer fluorogold. Our findings indicate that transgene expression declined in dopamine neurons despite the persistence of virus, and the capacity to readminister vector to these neurons was limited.
Gonzalez
Sarah C
SC
Department of Physiology Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK.
McMenamin
Margaret M
MM
Charlton
Harry M
HM
Goodman
James
J
Lantos
Tibor
T
Simpson
Christine
C
Wood
Matthew J A
MJ
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics; D004298:Dopamine / Q000502:physiology*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D007150:Immunohistochemistry; D007763:Lac Operon / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008845:Microinjections; D009474:Neurons / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013238:Stereotaxic Techniques; D013378:Substantia Nigra / Q000502:physiology; D019076:Transgenes / Q000502:physiology
D004279:DNA, Viral; D004298:Dopamine