DNA sequences encoding mutant antiviral regulatory proteins
US5686601A · kind A · utility
Assignee
Inventor
Key dates
| Filing date | Feb 18, 1993 |
| Grant date | Nov 11, 1997 |
| Priority date | — |
| Expiry date | Feb 18, 2013 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC12N2710/16622
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
Dominant negative or trans-dominant mutants of viral proteins represent a new and exciting means of antiviral therapy. However, the extreme specificity of a given dominant negative mutant limits its general utility in treating a broad spectrum of viral diseases, since it can typically interfere with the activity of only a single viral polypeptide encoded by a single virus. A dominant negative mutant of a gene encoding promiscuous viral transactivator protein was isolated in an attempt to generate a polypeptide which could inhibit gene expression and, therefore, virus replication nonspecifically. This mutant, a truncated derivative of the gene encoding herpes simplex virus type 1 (HSV-1) regulatory protein ICP0, was found to behave as a powerful repressor of gene expression from an assortment of HSV-1 and non-HSV-1 promoters in transient expression assays. Unexpectedly, it was also capable of inhibiting the replication of both HSV- 1 and a completely unrelated virus, human immunodeficiency virus, in cell culture. Moreover, a derivative of ICP0 with dominant mutant properties similar to that of pD19T can potentially be created by a failure to splice out the intron 2 sequences; transl…
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