Transgene Expression up to 7 Years in Nonhuman Primates Following Hepatic Transduction with Helper-Dependent Adenoviral Vectors
Transgene Expression up to 7 Years in Nonhuman Primates Following Hepatic Transduction with Helper-Dependent Adenoviral Vectors
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DOI：
10.1089/hum.2013.071
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发表时间：
2013-08-01
影响因子：
4.2
通讯作者：
Ng, Philip
中科院分区：
文献类型：
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作者：
Brunetti-Pierri, Nicola;Ng, Thomas;Ng, Philip
辅助病毒依赖性腺病毒载体（HDAd）已经显示出比第一代腺病毒载体介导相当长的转基因表达持续时间。我们以前已经表明，转基因表达HDAd转导的肝细胞可以持续高水平长达2.6年的非人灵长类动物后，单一载体管理。由于转基因表达的持续时间和长期毒性对于风险：获益评估至关重要，因此我们继续监测这些动物。我们在这里报告说，转基因表达已持续了长达7年的整个观察期的所有动物没有长期的不良影响。然而，在所有情况下，转基因表达水平随时间缓慢下降，到观察期结束时低于峰值的10%，但仍高于基线值2.3-111倍。这些结果将为临床应用HDAd前进行更知情的风险：获益评估提供重要信息。
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.