Gene therapy using SV40-derived vectors: What does the future hold?

Abstract

Effective genetic therapy requires both a fragment of genetic material to be used therapeutically and a means to deliver it. We began to study simian virus-40 (SV40) as a vector for gene transfer because available gene delivery vehicles did not provide for the full range of therapeutic uses. Other vectors are variably limited by immunogenicity, difficulties in production, restricted specificity, low titers, poor transduction efficiency, etc. In theory recombinant viral vectors based on SV40 (rSV40) should not, on the other hand, be similarly constrained. rSV40 vectors are easily manipulated and produced at very high titer, stable, lacking in immunogenicity, and capable of providing sustained high levels of transgene expression in both resting and dividing cells. The principle limitation of SV40-derived vectors is the size of the packageable insert (≤5 kb). The rationale for developing SV40 as a gene therapy vector is reviewed. Our studies with rSV40 gene transfer have focused mostly on hematopoietic progenitor cells (CD341) and their derivatives, and on gene delivery to the liver. In both settings, in vitro and in vivo, SV40 has proven to be very effective. It is thus a promising gene delivery vehicle that can complement others currently in use or under development. © 1999 Wiley-Liss, Inc.