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

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.

FIG. 1.

Serum bAFP levels in baboons injected with HDAd expressing bAFP from a liver-specific promoter. HDAd was administered by (A) Method 1, (B) Method 2, and (C and D) Method 3. Closed symbols represent data from the original publications. Open symbols represent new, follow-up data. bAFP, baboon alpha-fetoprotein; HDAd, helper-dependent adenoviral vectors.