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http://dx.doi.org/10.4333/KPS.2003.33.4.267

EBV-Based Plasmid Encoding HSV-TK for Cytocidal Gene Therapy  

Oh, Sang-Taek (Research Institute of Immunobiology, Catholic Research Institutes of Medical Science, Catholic University)
Min, Kyoung-Ah (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University)
Kim, Chong-Kook (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University)
Lee, Suk-Kyeong (Research Institute of Immunobiology, Catholic Research Institutes of Medical Science, Catholic University)
Publication Information
Journal of Pharmaceutical Investigation / v.33, no.4, 2003 , pp. 267-272 More about this Journal
Abstract
Herpes simplex virus (HSV) thymidine kinase (TK) has been widely used for suicidal gene therapy in combination with nucleoside analogs such as ganciclovir (GCV). The use of HSV-TK is limited due to the side effect of GCV at high concentrations. Previous studies showed that stable transfectants of mutant HSV-TK with enhanced affinity to GCV were killed at lower GCV concentrations. In this study, we tested whether mutant HSV-TK can provide enhanced suicidal effect when transiently transfected with Epstein-Barr virus (EBV)-based plasmid. EBV-based plasmid which contains OriP and EBNA-1 sequence is well known for a stable episomal maintenance in human cells. Optimal transfection condition was assessed for SNU-638 gastric cancer cell line using polyetylnimine (PEI). Maximum transfection efficiency was achieved when DNA:PEI was 1:3 (w/v). Cytotoxicities of mutant and wild type HSV-TK were compared before and after partially selecting transfected cells. The cells were sensitive to $100\;{\mu}g/ml$ hygromycin. Following GCV treatment, more cells were killed after hygromycin selection than before selection. The mutant HSV-TK showed enhanced cytotoxicity compared with the wild type HSV-TK. Our results suggest that the EBV-based plasmid encoding mutant HSV-TK may be useful to treat the diseases caused by uncontrolled cell proliferation such as cancer and rheumatoid arthritis.
Keywords
Herpes simplex Virus-Thymidine kinase; EBV-Based plasmid; Gene therapy; Polyethylenimine;
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