The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
Creation of drug-specific herpes simplex virus type 1 thymidine kinase mutants for gene therapy.
Open accessAbstract
Herpes simplex virus type 1 (HSV-1) thymidine kinase is currently used as a suicide agent in the gene therapy of cancer. This therapy is based on the preferential phosphorylation of nucleoside analogs by tumor cells expressing HSV-1 thymidine kinase. However, the use of HSV-1 thymidine kinase is limited in part by the toxicity of the nucleoside analogs. We have used random sequence mutagenesis to create new HSV-1 thymidine kinases that, compared with wild-type thymidine kinase, render cells much more sensitive to specific nucleoside analogs. A segment of the HSV-1 thymidine kinase gene at the putative nucleoside binding site was substituted with random nucleotide sequences. Mutant enzymes that demonstrate preferential phosphorylation of the nucleoside analogs, ganciclovir or acyclovir, were selected from more than one million Escherichia coli transformants. Among the 426 active mutants we have isolated, 26 demonstrated enhanced sensitivity to ganciclovir, and 54 were more sensitive to acyclovir. Only 6 mutant enzymes displayed sensitivity to both ganciclovir and acyclovir when expressed in E. coli. Analysis of 3 drug-sensitive enzymes demonstrated that 1 produced stable mammalian cell transfectants that are 43-fold more sensitive to ganciclovir and 20-fold more sensitive to acyclovir.
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Cites
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Selective Ablation of Proliferating Microglial Cells Exacerbates Ischemic Injury in the Brain
Lalancette-Hébert, M., Gowing, G., Simard, A., Weng, Y. C., & Kriz, J. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5360-06.2007 · Cited by 874
Experimental autoimmune encephalomyelitis repressed by microglial paralysis
Heppner, F. L., Greter, M., Marino, D., Falsig, J., Raivich, G., Hövelmeyer, N., Waisman, A., Rülicke, T., Prinz, M., Priller, J., et al. (2005) · Nature Medicine · doi:10.1038/nm1177 · Cited by 732
Gambhir, S. S., Barrio, J. R., Phelps, M. E., Iyer, M., Namavari, M., Satyamurthy, N., Wu, L., Green, L. A., Bauer, E., MacLaren, D. C., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.5.2333 · Cited by 450
Gambhir, S. S., Bauer, E., Black, M. E., Liang, Q., Kokoris, M. S., Barrio, J. R., Iyer, M., Namavari, M., Phelps, M. E., & Herschman, H. R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.6.2785 · Cited by 450
Self-citationImaging Transgene Expression with Radionuclide Imaging Technologies
Gambhir, S. S., Herschman, H. R., Cherry, S. R., Barrio, J. R., Satyamurthy, N., Toyokuni, T., Phelps, M. E., Larson, S. M., Balatoni, J., Finn, R., et al. (2000) · Neoplasia · doi:10.1038/sj.neo.7900083 · Cited by 358
Metadata
- Authors
- Black, M. E., Newcomb, T. G., Wilson, H. M., & Loeb, L. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1996-04-16
- Volume
- 93
- Issue
- 8
- Pages
- 3525-3529
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1992322591
- Cited by
- 275
- References
- 17
- FWCI
- 7.82
- Type
- journal article
- Language
- en
- Open access
- green
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- Black, M. E., Newcomb, T. G., Wilson, H. M., & Loeb, L. A. (1996). Creation of drug-specific herpes simplex virus type 1 thymidine kinase mutants for gene therapy. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.93.8.3525
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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