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• W2026734599 abstract "Abstract Background Adenoviral (Ad) vectors are one of the most widely used tools for modelling gene therapy strategies. However, they have not been used in long‐term models of neurological disease, as the period of time for which they mediate strong transgene expression is limited and/or variable. In this study we investigated the longevity of transgene expression in the brain when the powerful neuron‐specific Ad‐synapsin (Sy)‐EGFP‐woodchuck hepatitis virus post‐transcriptional regulatory element (WPRE) vector cassette is used at titres that do not elicit an immune response. Methods Adenoviral vectors expressing enhanced green fluorescent protein (EGFP) under the control of either the hCMV, hCMV‐WPRE, Sy or Sy‐WPRE promoter were constructed. These vectors were injected into the dentate gyrus region of hippocampus and transgene expression and immune cell infiltration assessed by fluorescence microscopy and immunocytochemical techniques, respectively. Results The quantitative analysis of EGFP expression showed that there was no significant change in synapsin or synapsin‐WPRE driven transcription 9 months after injection when compared with expression levels obtained 3 days after injection. However, when the hCMV promoter or the hCMV‐WPRE promoter cassette drove transgene expression, there was a dramatic fall in expression levels and very little expression was seen 9 months post‐transfection. Conclusions This study shows that non‐integrating vectors can be used to mediate powerful, long‐term episomal transgene expression in neurones. This work has important implications for neuronal gene therapy and is of relevance to studies investigating memory, behaviour and neuronal gene function. Copyright © 2003 John Wiley & Sons, Ltd." @default.
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• W2026734599 date "2003-02-20" @default.
• W2026734599 modified "2023-10-10" @default.
• W2026734599 title "Long-term transgene expression can be mediated in the brain by adenoviral vectors when powerful neuron-specific promoters are used" @default.
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• W2026734599 doi "https://doi.org/10.1002/jgm.381" @default.
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