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|Title:||Improved neuronal transgene expression from an AAV-2 vector with a hybrid CMV enhancer/PDGF-β promoter||Authors:||Wang, C.Y.
|Issue Date:||Jul-2005||Citation:||Wang, C.Y., Guo, H.Y., Lim, T.M., Ng, Y.K., Neo, H.P., Hwang, P.Y.K., Yee, W.-C., Wang, S. (2005-07). Improved neuronal transgene expression from an AAV-2 vector with a hybrid CMV enhancer/PDGF-β promoter. Journal of Gene Medicine 7 (7) : 945-955. ScholarBank@NUS Repository. https://doi.org/10.1002/jgm.742||Abstract:||Background: Adeno-associated virus type 2 (AAV-2) vectors are highly promising tools for gene therapy of neurological disorders. After accommodating a cellular promoter, AAV-2 vectors are able to drive sustained expression of transgene in the brain. This study aimed to develop AAV-2 vectors that also facilitate a high level of neuronal expression by enhancing the strength of a neuron-specific promoter, the human platelet-derived growth factor β-chain (PDGF) promoter. Methods and results: A hybrid promoter approach was adopted to fuse the enhancer of human cytomegalovirus immediately early (CMV) promoter to the PDGF promoter. In cultured cortex neurons, AAV-2 vectors containing the hybrid promoter augmented transgene expression up to 20-fold over that mediated by titer-matched AAV-2 vectors with the PDGF promoter alone and 4-fold over the CMV enhancer/promoter. Injection of AAV-2 vectors with the hybrid promoter into the rat striatum resulted in neuron-specific transgene expression, the level of which was about 10-fold higher than those provided by the two control AAV-2 expression cassettes at 4 weeks post-injection and maintained for at least 12 weeks. Gene expression in the substantia nigra through possible retrograde transport of the AAV-2 vectors injected into the striatum was not obvious. After direct injection of AAV-2 vectors into the substantia nigra, transgene expression driven by the hybrid promoter was observed specifically in dopaminergic neurons and its level was about 3 and 17 times higher than that provided by the PDGF promoter alone and the CMV enhancer/promoter, respectively. Conclusions: Enhanced transgene capacity plus neuron-specificity of the AAV-2 vectors developed in this study might prove valuable for gene therapy of Parkinson's disease. Copyright © 2005 John Wiley & Sons, Ltd.||Source Title:||Journal of Gene Medicine||URI:||http://scholarbank.nus.edu.sg/handle/10635/100896||ISSN:||1099498X||DOI:||10.1002/jgm.742|
|Appears in Collections:||Staff Publications|
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