Virus-based vectors for gene expression in mammalian cells: SV40

Recombinant gene delivery vectors derived from Tag -deleted SV40 viruses (rSV40s) are potentially useful tools for transduction of many cell types, both in culture and in animals. Characteristically, these vectors: (i) can be made to very high titers (>10 12 infectious units/ml); (ii) infect almost all nucleated mammalian cell types, whether resting or dividing, with high efficiency such that selection is not necessary; (iii) integrate rapidly into the cellular genome and provide for permanent transgene expression without detectable diminution over time; (iv) lack immunogenicity, neither imparting antigenicity to transduced cells nor eliciting neutralizing immune responses against themselves and thus; (v) can be administered multiple times in vivo to normal, immunocompetent animals; (vi) can carry up to ≈5 kb of foreign DNA; and (vii) are safe. Recombinant SV40-derived vectors have been used with pol II promoters to deliver transgenes that encode intracellular, cell membrane, and secreted proteins. They have also been used with pol III promoters to deliver untranslated RNAs, including ribozymes, antisense, RNA decoys, and small inhibitory RNAs. Experimental therapeutic applications of these vectors have included inhibiting HIV in culture and in vivo ; delivering transgenes encoding important missing enzymes, in animal models of human diseases; protecting cells from free radical-induced damage; immunizing against lentiviral antigens; and manipulating the balance of neurotransmitters in the brain. These vectors are limited by their cloning capacity of 5 kb and by the fact that they do not easily express commonly used marker genes such as fluorescent proteins and β-galactosidase. Currently, human trials of rSV40 vectors are being planned.