Administration of helper-dependent adenoviral vectors and sequential delivery of different vector serotype for long-term liver-directed gene transfer in baboons

• DOI: 10.1073/pnas.96.22.12816
• Publication Date: 2002-07-26T14:44:19Z
• Authors: Núria Morral; Wanda O’Neal; Karen Rice; Michele Leland; Johanne Kaplan; Pedro A. Piedra; Heshan Zhou; Robin J. Parks; Rizwan Velji; Estuardo Aguilar-...; Samuel Wadsworth; Frank L. Graham; Stefan Kochanek; K. Dee Carey; Arthur L. Beaudet
• Keywords: Expression cassette; Helper virus

The efficiency of first-generation adenoviral vectors as gene delivery tools is often limited by the short duration transgene expression, which can be related to immune responses and toxic effects viral proteins. In addition, readministration usually ineffective unless animals are immunocompromised or a different adenovirus serotype used. Recently, devoid all coding sequences (helper-dependent gutless vectors) have been developed avoid expression mice, liver-directed transfer with AdSTK109, helper-dependent (Ad) vector containing human α 1 -antitrypsin (hAAT) gene, resulted in sustained for longer than 10 months negligible toxicity liver. present report, we examined AdSTK109 liver baboons compared it expressing hAAT. Transgene was approximately 3–5 vectors. contrast, administration year two three baboons. We also investigated feasibility circumventing humoral response virus sequential serotypes. found that ineffectiveness due an Ad5 overcome use Ad2-based These data suggest long-term transgenes should possible combining reduced immunogenicity