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Title: Development of hybrid promoters and viral vectors for improved gene delivery to the central nervous system
Keywords: gene therapy; central nervous system; Parkinson’s disease; hybrid promoter; adeno-associated virus; baculovirus.
Issue Date: 25-Jan-2006
Citation: WANG CHAOYANG (2006-01-25). Development of hybrid promoters and viral vectors for improved gene delivery to the central nervous system. ScholarBank@NUS Repository.
Abstract: The purpose of this study was to develop suitable delivery systems with novel promoters and viral vectors for gene therapy of disorders in the CNS, particularly Parkinsona??s disease and malignant glioma tumors. By adding the enhancer of cytomegalovirus immediate-early gene to the upstream of cellular promoters, hybrid CMV E/PDGF promoter and CMV E/GFAP promoter were constructed. Improved transcriptional activities and retained cell type specificities were observed by in vitro and in vivo gene delivery with viral vectors. The results showed that a neuron-specific, high level, and long-term transgene expression can be achieved with AAV-2 vector carrying the CMV E/PDGF promoter, while a high level, transient and neuron- or astrocyte-specific transgene can be observed with baculovirus vectors carrying the CMV E/PDGF promoter or CMV E/GFAP promoter. ITR-flanking improved the baculovirus-mediated transgene expression further. In conclusion, with hybrid promoters and viral vectors, this study provides useful delivery systems for gene therapy of disorders in the CNS.
Appears in Collections:Ph.D Theses (Open)

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