Long-term gene expression in dividing and nondividing cells using SV40-derived vectors

Abstract

Among the goals of gene therapy is long-term expression of delivered transgenes. Recombinant Tagdeleted SV40 vectors (rSV40s) are especially well suited for this purpose. rSV40s deliver transgene expression that endures for extended periods of time in tissue culture and in vivo, in both dividing and nondividing cells. These vectors are particularly effective in transducing some cell types that have been almost unapproachable using other gene delivery systems, such as quiescent hematopoietic progenitor cells and their differentiated derivatives. Other cellular targets include neurons, brain microglia, hepatocytes, dendritic cells, vascular endothelium, and others. Because rSV40s do not elicit neutralizing antibodies they are useful for in vivo gene delivery in settings where more than one administration may be desirable. The key characteristics of these vectors include their high production titers and therefore suitability for large cell pools, effectiveness in delivering intracellular proteins, and untranslated RNAs, maintenance of transgene expression at constant levels for extended times, suitability for constitutive or conditional promoters and for combinatorial gene delivery and ability to integrate into genomes of both dividing and nondividing cells.

Designing Heart Performance by Gene Transfer

“…Finally, other viral-based vectors such as EpsteinBarr, foamy, and simian virus 40 (SV40) (555,843,890) have also been reported for use in gene transfer studies but have not been included in this discussion for reasons of space, frequency of use, and a lack of a rich literature in cardiac transduction. This does not preclude these vectors, however, as viable options for cardiac gene transfer in future studies.…”

Current approaches to enhance CNS delivery of drugs across the brain barriers

“…35 These include HSV, 36 lentivirus, 37 retrovirus, 38 recombinant AAV (adeno-associated virus), 39 simian virus 40, 40,41 and helper-dependent adenovirus. 42 Moreover, hybrid viral vectors have been constructed to incorporate different viral elements with particular features in order to achieve reproducible and stable gene delivery to the brain.…”

Pseudovirions as Vehicles for the Delivery of siRNA

“…There are certain fundamental differences between in vitro -packaged vectors and the related, recombinant SV40 viral vectors (rSV40) described in the works of Strayer and Cordelier, among others (76). In 2003, Cordelier and colleagues (77) designed a recombinant SV40 vector that lacked T-ag sequences, but retained the SV40 capsid genes, as well as the origin of replication ( ori ) and packaging signal ( ses ), which overlap with the SV40 early promoter region.…”

“…These rSV40 vectors differ from in vitro -packaged vectors, which carry no viral sequences and have also been used in RNAi applications (described below), because they still carry viral coding sequences and so cannot be categorized as pseudovirions. rSV40 vectors whose structural genes have been removed, leaving only ori , ses , and the SV40 early-promoter (which is overlapped by ori and ses ) are also possible (76). …”