Chromosomal integration of adenoviral vector DNA in vivo

Sam Laurel Stephen, Eugenio Montini, Vijayshankar Ganesh Sivanandam, Muhseen Al-Dhalimy, Hans A. Kestler, Milton Finegold, Markus Grompe, Stefan Kochanek

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


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 languageEnglish (US)
Pages (from-to)9987-9994
Number of pages8
JournalJournal of virology
Issue number19
StatePublished - Oct 2010

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology


Dive into the research topics of 'Chromosomal integration of adenoviral vector DNA in vivo'. Together they form a unique fingerprint.

Cite this