Neuronal gene transfer by baculovirus-derived vectors accommodating a neurone-specific promoter

Abstract

Recombinant baculoviruses have been employed as gene delivery vectors for mammalian cells, including neurones, during recent years. The aim of the current study was to develop a new recombinant baculovirus vector capable of enhancing gene expression in neurones. A hybrid promoter constructed by fusing the enhancer of human cytomegalovirus (CMV) immediately early promoter to the human platelet-derived growth factor (PDGF) β-chain promoter was placed into a baculovirus expression cassette. In cultured neurones, baculovirus vectors containing the hybrid promoter augmented transgene expression up to 100-fold greater than that mediated by titre-matched baculovirus vectors with the PDGF promoter alone. Double immunostaining of tissue sections collected from the striatum and the retina injected with the new baculovirus vector demonstrated its specificity in driving gene expression almost exclusively in neurones, confirming the feasibility of using a tissue-specific promoter in the context of baculovirus vectors to provide cell type-specific transgene expression. The attributes of the new baculovirus vector might have practical implications for gene therapy in the nervous system.