Design of viral vectors for improved gene delivery

Abstract

We have constructed Herpes Simplex Virus Type-1 (HSV-1) based amplicon viral vector, whereby the gene expression is controlled by cell cycle events. The strategy of infiltrating the resected region with these therapeutic vectors that can be activated once the residual dormant tumor cells start to proliferate would represent potentially advantageous tools for cancer gene therapy. To differentiate between glial and non-glial proliferating cells, glial cell-specific promoter has been employed. Our results demonstrated that transgene expression conferred by either the HSV-1 amplicon plasmids or amplicon viral vectors is cell type-specific and proliferation-dependent both in vitro and in vivo. These vectors have also been shown to be effective at delivering therapeutic genes to actively proliferating tumor cells in glioma xenografts. To overcome problems such as inaccessible tumor regions, glioma-specific peptides were isolated using phage display technique as a potential targeting device to home to human glioma cells.