Abstract
Top of pageAbstract The baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV)-based vectors are emerging as a new type of gene delivery vehicles. However, gene therapy application of the virus is still in its infancy and no practically useful application in cancer therapy has yet been produced, even in preclinical animal studies. We have constructed a baculoviral expression cassette containing an engineered GFAP promoter to restrict gene expression to astrocytes. Using this recombinant baculovirus, we observed extended in vivo transgene expression in the rat brain at 90 days postinjection, by which time the gene expression from baculovirus vectors with the CMV promoter had already become undetectable. The astrocyte specificity of the GFAP promoter was well preserved, as demonstrated by immunohistological analysis of brain samples and an axonal retrograde transport assay. Also, this recombinant baculovirus provided significantly improvedtransgene expression in glioma cells, with almost 100% of cells being transduced in certain glioma cell lines. When used to produce the A-chain of diphtheria toxin intracellularly in a rat glioma xenograft model, the baculoviruses effectively suppressed tumor development. The new baculovirus vector circumvents some of the inherent problems associated with mammalian viral vectors and provides an additional option for cancer gene therapy.
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