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Titolo:
SELECTIVE AND RAPID UPTAKE OF ADENOASSOCIATED VIRUS TYPE-2 IN BRAIN
Autore:
BARTLETT JS; SAMULSKI RJ; MCCOWN TJ;
Indirizzi:
UNIV N CAROLINA,GENE THERAPY CTR,7119 THURSTON BLDG,CB 7352 CHAPEL HILL NC 27599 UNIV N CAROLINA,GENE THERAPY CTR CHAPEL HILL NC 27599 UNIV N CAROLINA,CYST FIBROSIS PULM RES CTR CHAPEL HILL NC 27599 UNIV N CAROLINA,DEPT PHARMACOL CHAPEL HILL NC 27599 UNIV N CAROLINA,CTR NEUROSCI CHAPEL HILL NC 27599 UNIV N CAROLINA,DEPT PSYCHIAT CHAPEL HILL NC 27599
Titolo Testata:
Human gene therapy
fascicolo: 8, volume: 9, anno: 1998,
pagine: 1181 - 1186
SICI:
1043-0342(1998)9:8<1181:SARUOA>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECOMBINANT ADENOASSOCIATED VIRUS; MAMMALIAN BRAIN; GENE-EXPRESSION; VECTORS; TRANSDUCTION; CELLS; INCREASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
16
Recensione:
Indirizzi per estratti:
Citazione:
J.S. Bartlett et al., "SELECTIVE AND RAPID UPTAKE OF ADENOASSOCIATED VIRUS TYPE-2 IN BRAIN", Human gene therapy, 9(8), 1998, pp. 1181-1186

Abstract

Recombinant adeno-associated virus (AAV) vectors effectively transferand express foreign genes in the brain. The transferred genes, however, are selectively expressed in neurons, and the cause of this specificity is not understood. To address this question, wild-type AAV-2 capsids were covalently labeled with the fluorophore, Cy3, and infused into the inferior colliculus or the hippocampus. Using antibodies to identify neurons (NeuN), astrocytes (GFAP), or oligodendrocytes (OX-42), clear neuron-specific uptake of the virus was observed as early as 6 min after the start of the infusion. By 30 min postinfusion, AAV particles were present in the nucleus of neurons, yet in both the inferior colliculus and hippocampus, a subset of neurons did not take up the virus particles. No AAV particles were found in astrocytes 1.5 min or 24 hr after virus infusion. Interestingly, 1 hr postinfusion, no AAV particles were found in microglia, yet by 24 hr postinfusion, a punctate pattern of AAV particles was found in microglia. To test whether virus uptake correlated with vector-transduced cells, an rAAV-CMV-GFP virus was infused. By 3 days postinfusion, GFP was localized to neuronal populations with no expression in astrocytes or microglia, similar to thatof fluorescent virus uptake. These findings demonstrate that in brain, AAV particles rapidly bind and enter primarily neurons with a pattern similar to that of in vivo vector transduction. In addition, these studies indicate that viral binding and uptake, independent of promotertropism, can explain the specificity of AAV brain transduction. Thus,this first description of AAV kinetic disposition in vivo should facilitate targeted application of this vector for human brain gene therapy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/08/20 alle ore 08:15:35