NDLI: Site-specific integration mediated by a hybrid adenovirus/adeno-associated virus vector.

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Site-specific integration mediated by a hybrid adenovirus/adeno-associated virus vector.

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Site-specific integration mediated by a hybrid adenovirus/adeno-associated virus vector.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Cortese, R. Graham, F. L. La Monica, N. Ciliberto, G. Recchia, A. Lamartina, S. Toniatti, C. Pieroni, L. Parks, R. J. Palombo, F. Colloca, S.
Description	Author Affiliation: Recchia A ( Istituto di Ricerche di Biologia Molecolare (IRBM) P. Angeletti, Via Pontina Kilometer 30,600, 00040 Pomezia, Rome, Italy.);
Abstract	Adenovirus (Ad) and adeno-associated virus (AAV) have attractive and complementary properties that can be exploited for gene transfer purposes. Ad vectors are probably the most efficient vehicles to deliver foreign genes both in vitro and in vivo. AAV exhibits the unique ability to establish latency by efficiently integrating at a specific locus of human chromosome 19 (AAVS1). Two viral elements are necessary for the integration at AAVS1: Rep68/78 and the inverted terminal repeats (AAV-ITRs). In this study, we report the development of two helper-dependent adenoviral (HD) vectors, one carrying the Rep78 gene, the other an AAV-ITR-flanked transgene. Although Rep proteins have been demonstrated to interfere with Ad replication, HD Rep78 vector was successfully amplified on serial passages in 293CRE4 cells with a yield of 50-100 transducing units per cell. DNA integration at the AAVS1 site also was demonstrated in hepatoma cells coinfected with the HD-expressing Rep78 and with the second HD vector carrying a transgene flanked by AAV-ITRs. The high transduction efficiency, large cloning capacity, and high titer of the HD, combined with the site-specific integration machinery provided by AAV-derived components, make the Ad/AAV hybrid viruses a promising vehicle for gene therapy.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	6
Volume Number	96
Language	English
Publisher	National Academy of Sciences
Publisher Date	1999-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adenoviridae DNA-Binding Proteins Dependovirus Gene Transfer Techniques Genetic Vectors DNA Helicases Genetics HeLa Cells In Situ Hybridization Molecular Sequence Data Reassortant Viruses Trans-Activators Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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