Transgene expression up to 7 years in nonhuman primates following hepatic transduction with helper-dependent adenoviral vectors

Hum Gene Ther. 2013 Aug;24(8):761-5. doi: 10.1089/hum.2013.071.


Helper-dependent adenoviral vectors (HDAd) have been shown to mediate a considerably longer duration of transgene expression than first-generation adenoviral vectors. We have previously shown that transgene expression from HDAd-transduced hepatocytes can persist at high levels for up to 2.6 years in nonhuman primates following a single-vector administration. Because duration of transgene expression and long-term toxicity are critical for risk:benefit assessment, we have continued to monitor these animals. We report here that transgene expression has persisted for the entire observation period of up to 7 years for all animals without long-term adverse effects. However, in all cases, transgene expression level slowly declined over time to less than 10% of peak values by the end of the observation period but remained 2.3-111-fold above baseline values. These results will provide important information for a more informed risk:benefit assessment before clinical application of HDAd.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Gene Expression*
  • Genetic Vectors / genetics*
  • Helper Viruses / genetics*
  • Liver / drug effects*
  • Papio
  • Time
  • Transduction, Genetic*
  • Transgenes / genetics*