A Preclinical Animal Model to Assess the Effect of Pre-existing Immunity on AAV-mediated Gene Transfer

• Published in: Molecular therapy Vol. 17; no. 7; pp. 1215 - 1224
• Main Authors: Li, Hua, Lin, Shih-Wen, Giles-Davis, Wynetta, Li, Yan, Zhou, Dongming, Xiang, Zhi Quan, High, Katherine A, Ertl, Hildegund CJ
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2009; Elsevier Limited; Nature Publishing Group
• Subjects: Adenoviridae - genetics; Adenoviridae - immunology; Adenoviruses; Animals; Antibodies; Antigens; B-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cell Line; Cytokines; Enzyme-Linked Immunosorbent Assay; Gene therapy; Gene Transfer Techniques; Genetic Vectors - genetics; Genetic Vectors - immunology; Genomes; Human subjects; Humans; Interferon; Killer Cells, Natural - immunology; Lymphocytes; Male; Mice; Mice, Inbred BALB C; Models, Animal; Original; Polymerase Chain Reaction; Tumor necrosis factor-TNF; Vectors (Biology); United States > US; Pennsylvania

Hepatic adeno-associated virus (AAV)-serotype 2–mediated gene transfer results in sustained transgene expression in experimental animals but not in human subjects. We hypothesized that loss of transgene expression in humans might be caused by immune memory mechanisms that become reactivated upon AAV...