Adeno-associated viral vector gene expression in the adult rat spinal cord following remote vector delivery.
The current investigation tests whether adeno-associated viral vectors (rAAV) undergo remote delivery to the spinal cord via peripheral nerve injection as previously demonstrated with adenoviral vectors. The sciatic nerves of adult rats (n = 10) were injected with either an rAAV (rAAVCMV-lacZ) or adenoviral (AdCMV-lacZ) vector (1.4 x 10(7) particles/ml). After 21 days, the rAAV group demonstrated significantly higher spinal cord viral expression than the adenoviral group (P < 0.024). A second group of rats was injected with rAAV expressing the green fluorescence protein (GFP) reporter gene. GFP was detected 21 days after unilateral sciatic nerve injection in the neurons of the dorsal root ganglion and spinal cord. The codistribution of the viral genome and transgene in CNS neurons was confirmed with in situ hybridization. In summary, rAAV genes are expressed in CNS neurons following peripheral nerve injection at levels exceeding those seen following remote adenovirus injection.
Boulis
Nicholas M
NM
Neurosurgery, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. boulisn@cf.org
Noordmans
Aaron J
AJ
Song
Debbie K
DK
Imperiale
Michael J
MJ
Rubin
Adam
A
Leone
Paola
P
During
Matthew
M
Feldman
Eva L
EL
D000818:Animals; D001370:Axonal Transport / Q000235:genetics; D003587:Cytomegalovirus / Q000235:genetics / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism / Q000821:virology; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D017930:Genes, Reporter / Q000235:genetics; D005814:Genes, Viral / Q000235:genetics; D005822:Genetic Vectors / Q000502:physiology*; D049452:Green Fluorescent Proteins; D007763:Lac Operon / Q000235:genetics; D008164:Luminescent Proteins; D009475:Neurons, Afferent / Q000378:metabolism / Q000821:virology; D010525:Peripheral Nerves / Q000378:metabolism / Q000821:virology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000378:metabolism / Q000821:virology; D013116:Spinal Cord / Q000378:metabolism / Q000821:virology*; D019076:Transgenes / Q000235:genetics
D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins