Use of a herpes thymidine kinase/neomycin phosphotransferase chimeric gene for metabolic suicide gene transfer

Détails

ID Serval
serval:BIB_A9DF1CFB10C7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Use of a herpes thymidine kinase/neomycin phosphotransferase chimeric gene for metabolic suicide gene transfer
Périodique
Cancer Gene Ther
Auteur(s)
Candotti F., Agbaria R., Mullen C. A., Touraine R., Balzarini J., Johns D. G., Blaese R. M.
ISSN
0929-1903 (Print)
ISSN-L
0929-1903
Statut éditorial
Publié
Date de publication
04/2000
Volume
7
Numéro
4
Pages
574-80
Langue
anglais
Notes
Candotti, F
Agbaria, R
Mullen, C A
Touraine, R
Balzarini, J
Johns, D G
Blaese, R M
eng
England
Cancer Gene Ther. 2000 Apr;7(4):574-80.
Résumé
Metabolic suicide gene transfer is widely applied for gene therapy of cancer, and retroviral vectors expressing the herpes simplex virus thymidine kinase (HSV-tk) gene are commonly used in clinical trials. Most of these vectors contain positive selectable markers that undoubtedly facilitate the determination of viral titer and the identification of high-titer producer clones. However, the presence of additional transcriptional units may result in reduced expression of the gene of interest. The use of fusion genes expressing bifunctional proteins may help to overcome this problem. We have constructed a retroviral vector carrying the TNFUS69 chimeric gene, which originates from the fusion of the HSV-tk and neomycin phosphotransferase II genes, and evaluated the functional expression of the encoded fusion protein. In vitro, expression of the fusion gene conferred to target cells both resistance to neomycin and selective sensitivity to the antiherpetic drugs ganciclovir and (E)-5-(2-bromovinyl)-2'-deoxyuridine. Cells transduced with the fusion gene, however, showed reduced ability to phosphorylate ganciclovir compared with cells expressing the native HSV-tk. Therefore, although the fusion gene may be used as a constituent of retroviral cassettes for positive and negative selection in vitro, its usefulness for suicide gene transfer applications in vivo may depend upon the possibility of using (E)-5-(2-bromovinyl)-2'-deoxyuridine in a clinical context.
Mots-clé
3T3 Cells, Adenocarcinoma, Animals, Antiviral Agents/*toxicity, Bromodeoxyuridine/*analogs & derivatives/toxicity, Colonic Neoplasms, Fibrosarcoma, Ganciclovir/pharmacokinetics/*toxicity, Genetic Vectors, Kanamycin Kinase/*genetics/metabolism, Mice, Mice, Inbred C57BL, Phosphorylation, Plasmids, Recombinant Fusion Proteins/biosynthesis, Retroviridae, Simplexvirus/enzymology/genetics, Thymidine Kinase/*genetics/metabolism, Transcription, Genetic, *Transfection, Tumor Cells, Cultured
Pubmed
Open Access
Oui
Création de la notice
01/11/2017 11:29
Dernière modification de la notice
20/08/2019 16:14
Données d'usage