Efficient transduction of neural cells in vitro and in vivo by a baculovirus-derived vector

Gene delivery to the central nervous system is central to the development o f gene therapy for neurological diseases. We developed a baculovirus-derive d vector, the Bac-CMV-GFP vector, containing a reporter gene encoding for t he green fluorescent protein (GFP) under the control of the cytomegalovirus (CMV) promoter. Two neuroblastomal cell lines and three human primary neur al cultures could be efficiently transduced. In all cases, addition of buty rate, an inhibitor of histone deacetylase, increased the level of expressio n in terms of the number of GFP-expressing cells and the intensity of fluor escence. The level of expression in a human telencephalic culture was over 50% of transduced cells with a multiplicity of infection of 25. GFP express ion was demonstrated to be genuine expression and not pseudotransduction of the reporter protein. Most interestingly, Bac-CMV-GFP could transduce neur al cells in vivo when directly injected into the brain of rodents and was n ot inactivated by the complement system. Thus, baculovirus is a promising t ool for gene transfer into the central nervous system both for studies of t he function of foreign genes and the development of gene therapy strategies .