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Titolo:
Immediate and long-term safety of recombinant adeno-associated virus injection into the nonhuman primate muscle
Autore:
Favre, D; Provost, N; Blouin, V; Blacho, G; Cherel, Y; Salvetti, A; Moullier, P;
Indirizzi:
CHU Nantes, Hotel Dieu, INSERM, ERM0105,Lab Therapie Genet, F-44035 Nantes01, France CHU Nantes Nantes France 01 Lab Therapie Genet, F-44035 Nantes01, France CHU Nantes, Hotel Dieu, INSERM, U437, F-44035 Nantes, France CHU Nantes Nantes France F-44035 u, INSERM, U437, F-44035 Nantes, France Ecole Natl Vet, INRA UR 703, Anat Pathol Lab, F-44000 Nantes, France EcoleNatl Vet Nantes France F-44000 Pathol Lab, F-44000 Nantes, France
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 6, volume: 4, anno: 2001,
pagine: 559 - 566
SICI:
1525-0016(200112)4:6<559:IALSOR>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
COAGULATION FACTOR-IX; ADENOASSOCIATED VIRUS; GENE-TRANSFER; INTRAMUSCULAR INJECTION; HEMOPHILIA-B; ERYTHROPOIETIN DELIVERY; CYSTIC-FIBROSIS; MAMMALIAN-CELLS; VECTOR; EXPRESSION;
Keywords:
gene therapy; adeno-associated virus; biodistribution; shedding; safety; skeletal muscle; nonhuman primate;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Moullier, P CHU Nantes, Hotel Dieu, INSERM, ERM0105,Lab Therapie Genet, Bat J Monnet,30 Ave J Monnet, F-44035 Nantes 01, France CHU Nantes Bat J Monnet,30 Ave J Monnet Nantes France 01 ance
Citazione:
D. Favre et al., "Immediate and long-term safety of recombinant adeno-associated virus injection into the nonhuman primate muscle", MOL THER, 4(6), 2001, pp. 559-566

Abstract

Previous studies on distribution and toxicity of viral vectors administered in monkeys indicated that the nonhuman primate model has a reasonable predictive value for clinical applications. In this study, eight macaques wereinjected intramuscularly with recombinant adeno-associated virus (rAAV) atdoses similar to those administered to hemophilia B patients, and followedto analyze the dissemination and shedding in biological samples and long-term persistence in distant organs. Following rAAV delivery, we found vectorgenome in various biological fluids for up to 6 days and infectious particles exclusively in the serum during the first 48-72 hours. rAAV sequences were detected in peripheral blood mononuclear cells (PBMC) for up to 10 months. At necropsy, 8 to 18 months after rAAV delivery, rAAV sequences were found in lymph nodes and livers but never in the gonads. Tissue examination, of liver in particular, showed no abnormalities. We concluded that during our experimental time frame, rAAV-mediated gene transfer into skeletal muscle of macaques seemed to be safe with respect to the recipient and the environment. However, it was associated with a transient viremia and the persistence of rAAV sequences in PBMC, lymph nodes, and liver, the long-term consequences of which remain unknown.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/02/20 alle ore 20:48:54