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

Nicola Brunetti-Pierri, Thomas Ng, David Iannitti, William Cioffi, Gary Stapleton, Mark Law, John Breinholt, Donna Palmer, Nathan Grove, Karen Rice, Cassondra Bauer, Milton Finegold, Arthur Beaudet, Charles Mullins, Philip Ng

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)761-765
Number of pages5
JournalHuman Gene Therapy
Volume24
Issue number8
DOIs
StatePublished - Aug 1 2013

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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