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Titolo:
SUCCESSFUL READMINISTRATION OF ADENOASSOCIATED VIRUS VECTORS TO THE MOUSE LUNG REQUIRES TRANSIENT IMMUNOSUPPRESSION DURING THE INITIAL EXPOSURE
Autore:
HALBERT CL; STANDAERT TA; WILSON CB; MILLER AD;
Indirizzi:
FRED HUTCHINSON CANC RES CTR,1100 FAIRVIEW AVE N,ROOM C2-023 SEATTLE WA 98109 FRED HUTCHINSON CANC RES CTR SEATTLE WA 98109 UNIV WASHINGTON,DEPT PEDIAT SEATTLE WA 98195 UNIV WASHINGTON,DEPT MED SEATTLE WA 98195 UNIV WASHINGTON,SCH MED,DEPT PATHOL SEATTLE WA 98195
Titolo Testata:
Journal of virology (Print)
fascicolo: 12, volume: 72, anno: 1998,
pagine: 9795 - 9805
SICI:
0022-538X(1998)72:12<9795:SROAVV>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADENOASSOCIATED VIRUS; GENE-EXPRESSION; AAV VECTOR; FACTOR-IX; TRANSDUCTION; MUSCLE; MICE; INTEGRATION; LIGAND; RECOMBINATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
38
Recensione:
Indirizzi per estratti:
Citazione:
C.L. Halbert et al., "SUCCESSFUL READMINISTRATION OF ADENOASSOCIATED VIRUS VECTORS TO THE MOUSE LUNG REQUIRES TRANSIENT IMMUNOSUPPRESSION DURING THE INITIAL EXPOSURE", Journal of virology (Print), 72(12), 1998, pp. 9795-9805

Abstract

The airway is an important target for gene transfer to treat cystic fibrosis and other diseases that affect the lung. We previously found that marker gene expression did not persist in the bronchial epitheliumfollowing adeno-associated virus (AAV) vector administration to the rabbit lung. In an attempt to promote continued expression, we tested repeat vector administration, but no additional transduction was observed, and the block to transduction correlated with the appearance of neutralizing antibodies to the viral capsid. Here we show that mice exhibit a similar response but that treatment with anti-CD40 ligand antibody (MR1) and a soluble CTLA4-immunoglobulin fusion protein (CTLA4Ig) at the time of primary AAV vector exposure allowed successful repeat transduction and prevented production of neutralizing antibodies. We also tested the possibility that an immune response caused the loss of marker-positive cells in the epithelial population in rabbits by evaluating AAV vector expression in immunocompetent and immunodeficient mice. In contrast to results in rabbits, marker protein expression persisted in the lung in both groups of mice. AAV vector transduction occurredin alveolar cells, airway epithelial cells, and smooth muscle cells, and vector expression persisted for at least 8 months. Although data on persistence of AAV vector expression in the human lung are not available, it is likely that repeat transduction will be necessary either due to loss of expression or to the need for repeat administration to deliver effective amounts of AAV vectors. Results presented here indicate that transient immunosuppression will allow such repeat vector treatment of the lung.

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Documento generato il 26/05/20 alle ore 09:56:25