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.
Original language | English (US) |
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Pages (from-to) | 9987-9994 |
Number of pages | 8 |
Journal | Journal of virology |
Volume | 84 |
Issue number | 19 |
DOIs | |
State | Published - Oct 2010 |
ASJC Scopus subject areas
- Microbiology
- Immunology
- Insect Science
- Virology