Baculoviruses as Vectors for Gene Therapy against Human Prostate Cancer

Abstract

Current curative strategies for prostate cancer are restricted to the primary tumour, and the effect of treatments to control metastatic disease is not sustained. Therefore, the application of gene therapy to prostate cancer is an attractive alternative. Baculoviruses are highly restricted insect viruses, which can enter, but not replicate in mammalian cells. Baculoviruses can incorporate large amounts of extra genetic material, and will express transgenes in mammalian cells when under the control of a mammalian or strong viral promoter. Successful gene delivery has been achieved both in vitro and in vivo and into both dividing and nondividing cells, which is important since prostate cancers divide relatively slowly. In addition, the envelope protein gp64 is sufficiently mutable to allow targeted transduction of particular cell types. In this review, the advantages of using baculoviruses for prostate cancer gene therapy are explored, and the mechanisms of viral entry and transgene expression are described.

Process control in cell culture technology using dielectric spectroscopy

“…In medicine, viruses can serve to prepare vaccines, but are also an element of gene therapy [Alexander et al, 2007, Edelstein, et al, 2007, Stanbridge, et al, 2003. These viruses are mainly produced in mammalian packaging cell lines [Merten, 2004] or in insect cell lines using baculovirus [Negrete et al, 2007, Stanbridge et al, 2003].…”

“…These viruses are mainly produced in mammalian packaging cell lines [Merten, 2004] or in insect cell lines using baculovirus [Negrete et al, 2007, Stanbridge et al, 2003]. The same cell culture system can be used to produce recombinant proteins for vaccines.…”

“…Whole cells may also be the target product for example in stem cell therapy [Weber et al, 2007b]. Insect cells, which are for example used for the production of recombinant proteins, viruses or viral components [Nehring et al, 2006] are currently gaining an increased importance in the field of regenerative medicine Kotin, 2008, Stanbridge et al, 2003], especially in gene therapy [Alexander et al, 2007, Edelstein et al, 2007, Stanbridge, et al, 2003. Cells may be grown in suspension, on surfaces, or even in threedimensional solid matrices.…”

Astrocytic expression of transgene in the rat brain mediated by baculovirus vectors containing an astrocyte-specific promoter

“…40 Different from animal viruses, baculovirus infection does not lead to expression of its own genes or viral replication in mammalian cells. 4,41,42 As a result, even though certain sequences of the virus can function as promoters or enhancers of transcription in insect cells, they will be silent in mammalian cells owing to the absence of supporting factors, and are less likely to have an effect on the cell-type specificity of a mammalian promoter inserted into a baculovirus vector.…”

Prostate Cancer Evaluation: Design, Synthesis, and Evaluation of Novel Enzyme-Activated Proton MRI Contrast Agents

“…[11][12][13][14][15][16] However, there are major issues in terms of assessing the delivery to target tissue, assessing the uniformity (versus heterogeneity) of biodistribution and determining whether the genes are expressed. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] A viral construct is often readministered on successive occasions, but this should optimally be timed to coincide with loss of expression. Inevitably gene therapy has associated risks, and thus non-invasive in vivo determining the duration of gene expression in an individual tumor could greatly enhance the viability of the approach.…”