Functional expression of thymidine kinase in human leukaemic and colorectal cells, delivered as EGFP fusion protein by herpesvirus saimiri-based vector

Cancer Gene Therapy
Jennifer H HoggarthD M Meredith

Abstract

Herpesvirus saimiri (HVS) has the capacity to incorporate large amounts of heterologous DNA and can infect many different human cell types. To develop its potential as a gene therapy vector, we cloned herpes simplex virus thymidine kinase (TK) gene into the HVS genome in the form of an enhanced green fluorescent protein (EGFP) fusion protein, using a cosmid-based approach. At multiplicity of infection = 100 over 90% of human leukemic K562 and Jurkat cells were transduced with HVS/EGFP-TK. Conditions of no selective pressure expression were maintained at > 92% per cell division. Expression of the EGFP-TK fusion protein rendered transfected leukaemic cells sensitive to cytotoxic treatment with the prodrugs ganciclovir (GCV) and (E)-5-(2-bromovinyl)-2'deoxyuridine (BVDU) at concentrations as low as 10 ng/ml. The viral vector was also screened against a panel of colorectal and pancreatic carcinoma cell lines. All cell lines were transduced but showed a range of sensitivity to infection. Three of the most easily transduced cell lines: Mia PaCa, HCT116 and SW948 transduced with HVS/EGFP-TK were effectively ablated by subsequent treatment with GCV or BVDU. Our results show that in its current form HVS/EGFP-TK could be utilized as an a...Continue Reading

References

Oct 1, 1992·Current Opinion in Biotechnology·R K Naviaux, I M Verma
Apr 1, 1989·Journal of Virology·R Grassmann, B Fleckenstein
Jan 1, 1985·European Journal of Pediatrics·Y BenoitE De Clercq
Apr 1, 1983·Antimicrobial Agents and Chemotherapy·J R WingardW H Burns
Sep 1, 1983·The Journal of Antimicrobial Chemotherapy·G B Elion
Apr 1, 1984·European Journal of Cancer & Clinical Oncology·J Wildiers, E De Clercq
Jan 28, 1998·Journal of Virology·S M DuboiseJ U Jung
Sep 12, 2000·Journal of Hematotherapy & Stem Cell Research·E A Frolova-JonesD M Meredith
Oct 21, 2000·Molecular Pathology : MP·K M KurianA H Wyllie
Oct 29, 2000·Advances in Virus Research·M M Hitt, F L Graham
Mar 10, 2001·Journal of Cellular Physiology·O Greco, G U Dachs
Jul 16, 2002·Memórias do Instituto Oswaldo Cruz·G S MagalhaesA M Ventura
Aug 23, 2002·Protein Science : a Publication of the Protein Society·Mark S Kokoris, Margaret E Black
Nov 5, 2002·The Journal of Clinical Endocrinology and Metabolism·Luisa BarzonGiorgio Palù
Dec 3, 2002·Journal of Medicinal Chemistry·Sven GuentherVasu Nair
Jan 25, 2003·BMJ : British Medical Journal·Charles Marwick

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Citations

Mar 16, 2013·Journal of Anaesthesiology, Clinical Pharmacology·Sameer Gupta, Robert Atcheson

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