SV40-based gene therapy vectors: turning an adversary into a friend.

For gene delivery to be of use, a situation suitable for delivery of genetic material, a specific genetic construct to be delivered and the appropriate means to deliver it are required. Simian virus-40 (SV40) gene therapy vectors for gene transfer may be an important advance in the latter category. While other vectors are variably limited for example by immunogenicity, difficulties in production, restricted specificity, low titers, poor transduction efficiency, etc., recombinant viral vectors based on SV40 (rSV40) should not be similarly constrained. They are easily manipulated and produced at very high titer, stable, apparently lacking in immunogenicity, and capable of providing sustained high levels of transgene expression in almost any cell type, whether resting or dividing. The major limitation of SV40-derived vectors is packaging capacity, which restricts insert sizes. The rationale for developing SV40 as a gene therapy vector is reviewed, based on what is known of wild-type SV40. Studies with rSV40 gene transfer have focused mostly on hematopoietic progenitor cells (CD34+) and their derivatives, and on gene delivery to the liver. In both settings, in vitro and in vivo, SV40 has been very effective. It is therefore a highly promising gene delivery vehicle that may complement other vectors that are currently in use or that are being developed.