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Influence of promoter and WHV post-transcriptional regulatory element on AAV-mediated transgene expression in the rat brain
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Influence of promoter and WHV post-transcriptional regulatory element on AAV-mediated transgene expression in the rat brain
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Influence of promoter and WHV post-transcriptional regulatory element on AAV-mediated transgene expression in the rat brain
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Journal Article
Influence of promoter and WHV post-transcriptional regulatory element on AAV-mediated transgene expression in the rat brain
2000
Overview
Recombinant adeno-associated viruses (rAAVs) can transduce several tissues, including the brain. However, in brain the duration of gene expression in different areas is variable, which has been ascribed to viral (CMV) promoter silencing in some regions over time. We have compared expression of enhanced green fluorescent protein (EGFP) in the nigrostriatal pathway of rats mediated by rAAVs containing the CMV or platelet-derived growth factor-beta chain (PDGF-beta) promoter. In addition, we studied the effects of the woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) on transgene expression in vivo. The rAAV vectors containing the neuron-specific PDGF-beta chain promoter transduced significantly more dopaminergic neurons than titer-matched vectors carrying the CMV promoter. Moreover, the WPRE further increased EGFP expression, and a rAAV vector incorporating both the PDGF-beta chain promoter and the WPRE resulted in efficient EGFP expression in dopaminergic neurons and their projections in the striatum for at least 41 weeks after virus injection. Our results emphasize the importance of a strong tissue-specific promoter in achieving optimal transgene expression, not only in long-term but also in short-term studies where viral titers may be limiting. Furthermore, they suggest that incorporation of the WPRE into rAAVs, and possibly other types of vectors, is useful to enhance transgene expression in vivo.
Publisher
Nature Publishing Group
Subject
/ Animals
/ Biological and medical sciences
/ Fundamental and applied biological sciences. Psychology
/ Genetic Vectors - administration & dosage
/ Health. Pharmaceutical industry
/ Hepatitis B Virus, Woodchuck - genetics
/ Industrial applications and implications. Economical aspects
/ Luminescent Proteins - genetics
/ Male
/ Platelet-derived growth factor
/ Platelet-Derived Growth Factor - genetics
/ Rats
/ Regulatory Sequences, Nucleic Acid
/ Viruses
