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

Academic Article

Abstract

  • 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. © Copyright 2013, Mary Ann Liebert, Inc. 2013.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Brunetti-Pierri N; Ng T; Iannitti D; Cioffi W; Stapleton G; Law M; Breinholt J; Palmer D; Grove N; Rice K
  • Start Page

  • 761
  • End Page

  • 765
  • Volume

  • 24
  • Issue

  • 8