Chromosomal integration of adenoviral vector DNA in vivo

J Virol. 2010 Oct;84(19):9987-94. doi: 10.1128/JVI.00751-10. Epub 2010 Aug 4.


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(Deltaexon5) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Base Sequence
  • Chromosomes / genetics*
  • Chromosomes / virology*
  • DNA Primers / genetics
  • DNA, Viral / genetics*
  • Gene Transfer Techniques
  • Genetic Vectors*
  • Hydrolases / genetics
  • Hydrolases / metabolism
  • Liver / virology
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombination, Genetic
  • Virus Integration / genetics*


  • DNA Primers
  • DNA, Viral
  • Recombinant Proteins
  • Hydrolases
  • fumarylacetoacetase