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ABSTRACT: Baculoviruses have proven capacity for the production of recombinant proteins including virus-like particles and as viral vectors. Recent progress in preclinical studies suggest that baculoviruses have potential as new vectors for gene therapy but so far no clinical trials have been performed. To date, no specific guidelines for the use of baculoviruses as human gene therapy vectors exist but researchers can utilize existing guidelines made for other biological products. Because of the long history of research on baculoviruses, a lot of knowledge has been obtained that forms a good basis for the gene therapy development process. This article gives an overview of the current status of the application of baculovirus vectors in gene therapy and summarizes some of the challenges to overcome before the first clinical trials with baculoviruses can be accomplished.
Journal of Invertebrate Pathology 07/2011; 107 Suppl:S106-12. · 2.06 Impact Factor
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ABSTRACT: Baculovirus expression vector system (BEVS) is well known as a feasible and safe technology to produce recombinant (re-)proteins in a eukaryotic milieu of insect cells. However, its proven power in gene delivery and gene therapy is still poorly recognized. The basis of BEVS lies in large enveloped DNA viruses derived from insects, the prototype virus being Autographa californica multiple nucleopolyhedrovirus (AcMNPV). Infection of insect cell culture with a virus encoding a desired transgene under powerful baculovirus promoter leads to re-protein production in high quantities. Although the replication of AcMNPV is highly insect specific in nature, it can penetrate and transduce a wide range of cells of other origin. Efficient transduction requires only virus arming with an expression cassette active in the cells under investigation. The inherent safety, ease and speed of virus generation in high quantities, low cytotoxicity and extreme transgene capacity and tropism provides many advantages for gene delivery over the other viral vectors typically derived from human pathogens.
Methods in molecular biology (Clifton, N.J.) 01/2011; 737:279-301.
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ABSTRACT: Baculoviruses are safe and high-capacity vectors for gene delivery which have matured from the initial successful experiments performed in liver cells into convenient tools to transduce almost any cell from any origin in vitro and ex vivo. This is a result of 15 years of intensive vector development as well as studies performed in vertebrate cells to reveal important factors affecting the transduction efficacy. Now, at the stage when the first evidence of meaningful use of baculoviruses for therapeutic applications has been reported, there is no doubt that the technology will meet the expectations as highly useful platform for many applications of gene delivery. This review summarizes the pre-clinical in vivo work carried out with baculoviruses and discusses remaining challenges which still need to be solved.
Current Gene Therapy 04/2010; 10(3):187-94. · 3.39 Impact Factor
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ABSTRACT: Baculoviruses can express transgenes under mammalian promoters in a wide range of vertebrate cells. However, the success of transgene expression is dependent on both the appropriate cell type and culture conditions. We studied the mechanism behind the substantial effect of the cell culture medium on efficiency of the baculovirus transduction in different cell lines. We tested six cell culture mediums; the highest transduction efficiency was detected in the presence of RPMI 1640 medium. Vimentin, a major component of type III intermediate filaments, was reorganized in the optimized medium, which associated with enhanced nuclear entry of baculoviruses. Accordingly, the phosphorylation pattern of vimentin was changed in the studied cell lines. These results suggest that vimentin has an important role in baculovirus entry into vertebrate cells. Enhanced gene delivery in the optimized medium was observed also with adenoviruses and lentiviruses. The results highlight the general importance of the culture medium in the assembly of the cytoskeleton network and in viral gene delivery.
Journal of biotechnology 11/2009; 145(2):111-9. · 2.88 Impact Factor
