Homologous and heterologous recombination between adenovirus vector DNA and chromosomal DNA

2008 ◽  
Vol 10 (11) ◽  
pp. 1176-1189 ◽  
Author(s):  
Sam Laurel Stephen ◽  
Vijayshankar Ganesh Sivanandam ◽  
Stefan Kochanek
Keyword(s):  
Adenovirus Vector ◽  
Chromosomal Dna ◽  
Vector Dna

scholarly journals 852. Chromatin Study of Adenovirus Vector DNA In Vivo

2006 ◽  
Vol 13 ◽  
pp. S329
Author(s):  
Dan Cao ◽  
Mark A. Kay
Keyword(s):  
Adenovirus Vector ◽  
Vector Dna

scholarly journals Chromosomal Integration of Adenoviral Vector DNA In Vivo

2010 ◽  
Vol 84 (19) ◽  
pp. 9987-9994 ◽  
Author(s):  
Sam Laurel Stephen ◽  
Eugenio Montini ◽  
Vijayshankar Ganesh Sivanandam ◽  
Muhseen Al-Dhalimy ◽  
Hans A. Kestler ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Adenoviral Vector ◽  
High Capacity ◽  
Median Frequency ◽  
Chromosomal Dna ◽  
Genomic Locus ◽  
Vector Integration ◽  
Fumarylacetoacetate Hydrolase ◽  
Vector Dna

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 FAHΔexon5 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 × 10−5 per transduced hepatocyte, while homologous recombination occurred more rarely with a median frequency of 3.88 × 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.

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