Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.ymthe.2006.05.020
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dc.titleGAL4-NF-κB Fusion Protein Augments Transgene Expression from Neuronal Promoters in the Rat Brain
dc.contributor.authorLiu, B.H.
dc.contributor.authorYang, Y.
dc.contributor.authorPaton, J.F.R.
dc.contributor.authorLi, F.
dc.contributor.authorBoulaire, J.
dc.contributor.authorKasparov, S.
dc.contributor.authorWang, S.
dc.date.accessioned2014-10-27T08:29:06Z
dc.date.available2014-10-27T08:29:06Z
dc.date.issued2006-12
dc.identifier.citationLiu, B.H., Yang, Y., Paton, J.F.R., Li, F., Boulaire, J., Kasparov, S., Wang, S. (2006-12). GAL4-NF-κB Fusion Protein Augments Transgene Expression from Neuronal Promoters in the Rat Brain. Molecular Therapy 14 (6) : 872-882. ScholarBank@NUS Repository. https://doi.org/10.1016/j.ymthe.2006.05.020
dc.identifier.issn15250016
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/100732
dc.description.abstractTargeted gene expression mediated by a mammalian cellular promoter is desirable for gene therapy in the brain, where there are a variety of different neuronal phenotypes, several types of supportive cells, and blood vessels. However, this approach can be hampered by weak activity of some cellular promoters. In view of the potency of the transcription factor NF-κB in regulating neuronal gene expression, we have assessed whether it can be used to enhance the strength of neuron-specific promoters. Our approach was to use a neuronal promoter to drive expression of a chimeric transactivator, which consisted of a part of the transcriptional activation domain of the NF-κB p65 protein fused to the DNA-binding domain of GAL4 protein from yeast. The second copy of the neuronal promoter was modified by introducing the unique GAL4 binding sequences at its 5′ end and used to drive the expression of a transgene. Binding of the chimeric transcriptional activator upstream of the second promoter was expected to potentiate its transcriptional activity. In this study, the approach was applied to the platelet-derived growth factor β chain and synapsin-1 neuron-specific promoters and tested in vitro and in vivo using plasmid, lentiviral, and baculoviral vectors. We observed up to a 100-fold improvement in reporter gene expression in cultured neurons and 20-fold improvement in the rat brain in vivo. Moreover, the cell-type specificity of the two tested promoters was well preserved and restricted to neurons. Finally, the expression driven by the new lentiviral vectors with the p65-potentiated synapsin-1 promoter showed no signs of decline or cell damage 4 weeks after injection. This approach should be suitable for constructing powerful and stable gene expression systems based on weak cell-specific promoters in neuronal phenotypes. © 2006 The American Society of Gene Therapy.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1016/j.ymthe.2006.05.020
dc.sourceScopus
dc.subjectbrain
dc.subjectgene transfer
dc.subjectneuron-specific promoter
dc.subjectneurons
dc.subjecttranscriptional activity
dc.typeArticle
dc.contributor.departmentBIOLOGICAL SCIENCES
dc.description.doi10.1016/j.ymthe.2006.05.020
dc.description.sourcetitleMolecular Therapy
dc.description.volume14
dc.description.issue6
dc.description.page872-882
dc.description.codenMTOHC
dc.identifier.isiut000242723300014
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