Transduction characteristics of adeno-associated virus vectors expressing cap serotypes 7, 8, 9, and Rh10 in the mouse brain.
Recombinant adeno-associated viral (AAV) vectors can transduce cells of the CNS, resulting in long-term expression. AAV vector transduction varies depending on the serotype used and the region of the brain injected. AAV serotypes 7, 8, 9, and Rh10 have recently become available, but the transduction capabilities of these serotypes within the CNS have not been determined. We show that AAV 7, 8, 9, and Rh10 vectors expressing cDNA for a lysosomal enzyme transduce neurons, but not astrocytes or oligodendrocytes, in the cortex, striatum, hippocampus, and thalamus. Although all of the vectors contained the same genome, there were markedly different transduction patterns that could be due only to the differences in capsid proteins. The AAV 9 vector was found to undergo vector genome transport to distal neuronal cell bodies via known axonal pathways. This facilitated the distribution of enzyme, resulting in correction of lysosomal storage lesions in regions of a diseased brain that would not be corrected if the genome were not transported.
Cearley
Cassia N
CN
W. F. Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, and Division of Neurology, Stokes Research Institute, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Wolfe
John H
JH
D000818:Animals; D001369:Axons / Q000201:enzymology / Q000821:virology; D001921:Brain / Q000378:metabolism*; D002213:Capsid / Q000145:classification / Q000201:enzymology; D036022:Capsid Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D005966:Glucuronidase / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D016538:Mucopolysaccharidosis VII / Q000235:genetics / Q000628:therapy / Q000821:virology; D012333:RNA, Messenger / Q000378:metabolism; D012703:Serotyping; D014161:Transduction, Genetic; D019065:Virus Assembly / Q000235:genetics
D036022:Capsid Proteins; D012333:RNA, Messenger; D005966:Glucuronidase