E. coli nitroreductase/CB1954: in vitro studies into a potential system for feline cancer gene therapy.
Investigations were carried out to identify a suitable prodrug activating system for feline gene therapy with the eventual aim of treating feline thyroid disease and feline neoplasia. The E. coli nitroreductase (NTR)/CB1954 prodrug activating system was evaluated in vitro in feline cells by transient transfection with a nitroreductase expressing construct and subsequent treatment with the prodrug CB1954. The feline cells successfully expressed E. coli nitroreductase, which was able to activate the prodrug CB1954 resulting in cytotoxicity to both transformed and adjacent cells (a bystander effect) in vitro. In the absence of nitroreductase, CB1954 was non-toxic to feline cells. In addition, the nitroreductase gene was expressed in rat thyroid cells under the control of the cell type specific feline thyroglobulin promoter. This paper demonstrates that the E. coli nitroreductase/CB1954 system may be suitable for in vivo feline gene therapy, and further investigations are warranted.
Blackwood
L
L
Molecular Therapeutics Research Group, Small Animal Clinical Studies , Glawgow, UK. L.Blackwood@vet.gla.ac.uk
O'Shaughnessy
P J
PJ
Reid
S W
SW
Argyle
D J
DJ
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D001388:Aziridines / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D001483:Base Sequence; D015153:Blotting, Western / Q000662:veterinary; D002371:Cat Diseases / Q000628:therapy*; D002415:Cats; D003601:Cytotoxicity Tests, Immunologic / Q000662:veterinary; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel / Q000662:veterinary; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D015316:Genetic Therapy / Q000662:veterinary*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000628:therapy / Q000662:veterinary*; D009601:Nitroreductases / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000662:veterinary; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D001388:Aziridines; D017931:DNA Primers; D011355:Prodrugs; C100099:tretazicar; D009601:Nitroreductases