Long-term gene expression in dividing and nondividing cells using SV40-derived vectors.
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.
Strayer
David S
DS
Department of Pathology and Cell Biology, Jefferson Medical College, Philadelphia, PA, USA. david.strayer@jefferson.edu
Agrawal
Lokesh
L
Cordelier
Pierre
P
Liu
Bianling
B
Louboutin
Jean-Pierre
JP
Marusich
Elena
E
McKee
Hayley J
HJ
Ren
Carmen N NiGongyi
CN
Strayer
Marlene S
MS
D000818:Animals; D002455:Cell Division; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D016254:Mutagenesis, Insertional; D013539:Simian virus 40 / Q000235:genetics* / Q000276:immunology*; D016662:Virus Integration