Universität zu Köln

Stephen, Sam Laurel, Montini, Eugenio ORCID: 0000-0003-1771-6067, Sivanandam, Vijayshankar Ganesh, Al-Dhalimy, Muhseen, Kestler, Hans A. ORCID: 0000-0002-4759-5254, Finegold, Milton, Grompe, Markus ORCID: 0000-0002-6616-4345 and Kochanek, Stefan (2010). Chromosomal Integration of Adenoviral Vector DNA In Vivo. J. Virol., 84 (19). S. 9987 - 9995. WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 1098-5514

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Abstract

So far there has been no report of any clinical or preclinical evidence for chromosomal vector integration following adenovirus (Ad) vector-mediated gene transfer in vivo. We used liver gene transfer with high-capacity Ad vectors in the FAH(Delta exon5) mouse model to analyze homologous and heterologous recombination events between vector and chromosomal DNA. Intravenous injection of Ad vectors either expressing a fumarylacetoacetate hydrolase (FAH) cDNA or carrying part of the FAH genomic locus resulted in liver nodules of FAH-expressing hepatocytes, demonstrating chromosomal vector integration. Analysis of junctions between vector and chromosomal DNA following heterologous recombination indicated integration of the vector genome through its termini. Heterologous recombination occurred with a median frequency of 6.72 x 10(-5) per transduced hepatocyte, while homologous recombination occurred more rarely with a median frequency of 3.88 x 10(-7). This study has established quantitative and qualitative data on recombination of adenoviral vector DNA with genomic DNA in vivo, contributing to a risk-benefit assessment of the biosafety of Ad vector-mediated gene transfer.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Stephen, Sam Laurel UNSPECIFIED UNSPECIFIED UNSPECIFIED Montini, Eugenio UNSPECIFIED orcid.org/0000-0003-1771-6067 UNSPECIFIED Sivanandam, Vijayshankar Ganesh UNSPECIFIED UNSPECIFIED UNSPECIFIED Al-Dhalimy, Muhseen UNSPECIFIED UNSPECIFIED UNSPECIFIED Kestler, Hans A. UNSPECIFIED orcid.org/0000-0002-4759-5254 UNSPECIFIED Finegold, Milton UNSPECIFIED UNSPECIFIED UNSPECIFIED Grompe, Markus UNSPECIFIED orcid.org/0000-0002-6616-4345 UNSPECIFIED Kochanek, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-495924
DOI:	10.1128/JVI.00751-10
Journal or Publication Title:	J. Virol.
Volume:	84
Number:	19
Page Range:	S. 9987 - 9995
Date:	2010
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	1098-5514
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TYROSINEMIA TYPE-I; TRANSCRIPTION START REGIONS; EMBRYONIC STEM-CELLS; DE-NOVO METHYLATION; GENE-THERAPY; HUMAN GENOME; SPONTANEOUS MUTATION; CELLULAR DNA; FOAMY VIRUS; VIRAL-DNA Multiple languages Virology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49592