DOE Patents title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Selective destruction of cells infected with human immunodeficiency virus

Abstract

Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a variant of a protein synthesis inactivating toxin wherein a viral protease cleavage site is interposed between the A and B chains. The variant of the type II ribosome-inactivating protein is activated by digestion of the viral protease cleavage site by the specific viral protease. The activated ribosome-inactivating protein then kills the cell by inactivating cellular ribosomes. A preferred embodiment of the invention is specific for human immunodeficiency virus (HIV) and uses ricin as the ribosome-inactivating protein. In another preferred embodiment of the invention, the variant of the ribosome-inactivating protein is modified by attachment of one or more hydrophobic agents. The hydrophobic agent facilitates entry of the variant of the ribosome-inactivating protein into cells and can lead to incorporation of the ribosome-inactivating protein into viral particles. Still another preferred embodiment of the invention includes a targeting moiety attached to the variants of the ribosome-inactivating protein to target the agent to HIV infectable cells.

Inventors:
;
Issue Date:
Research Org.:
Idaho National Laboratory (INL), Idaho Falls, ID (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1174512
Patent Number(s):
6627197
Application Number:
09/785,921
Assignee:
Bechtel BWXT Idaho, LLC (Idaho Falls, ID)
Patent Classifications (CPCs):
A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
Y - NEW / CROSS SECTIONAL TECHNOLOGIES Y10 - TECHNICAL SUBJECTS COVERED BY FORMER USPC Y10S - TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
DOE Contract Number:  
AC07-94ID13223
Resource Type:
Patent
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Keener, William K., and Ward, Thomas E. Selective destruction of cells infected with human immunodeficiency virus. United States: N. p., 2003. Web.
Keener, William K., & Ward, Thomas E. Selective destruction of cells infected with human immunodeficiency virus. United States.
Keener, William K., and Ward, Thomas E. Tue . "Selective destruction of cells infected with human immunodeficiency virus". United States. https://www.osti.gov/servlets/purl/1174512.
@article{osti_1174512,
title = {Selective destruction of cells infected with human immunodeficiency virus},
author = {Keener, William K. and Ward, Thomas E.},
abstractNote = {Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a variant of a protein synthesis inactivating toxin wherein a viral protease cleavage site is interposed between the A and B chains. The variant of the type II ribosome-inactivating protein is activated by digestion of the viral protease cleavage site by the specific viral protease. The activated ribosome-inactivating protein then kills the cell by inactivating cellular ribosomes. A preferred embodiment of the invention is specific for human immunodeficiency virus (HIV) and uses ricin as the ribosome-inactivating protein. In another preferred embodiment of the invention, the variant of the ribosome-inactivating protein is modified by attachment of one or more hydrophobic agents. The hydrophobic agent facilitates entry of the variant of the ribosome-inactivating protein into cells and can lead to incorporation of the ribosome-inactivating protein into viral particles. Still another preferred embodiment of the invention includes a targeting moiety attached to the variants of the ribosome-inactivating protein to target the agent to HIV infectable cells.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Tue Sep 30 00:00:00 EDT 2003},
month = {Tue Sep 30 00:00:00 EDT 2003}
}

Works referenced in this record:

Ricin: structure, mode of action, and some current applications.
journal, February 1994


Preparation and characterization of recombinant proricin containing an alternative protease-sensitive linker sequence
journal, September 1992


Rationale for the Use of Immunotoxins in the Treatment of HIV-infected Humans
journal, January 1998


Bryodin, a single-chain ribosome-inactivating protein, selectively inhibits the growth of HIV-1-infected cells and reduces HIV-1 production
journal, December 1993


HIV-infected cells are killed by rCD4-ricin A chain
journal, November 1988


Recombinant proricin binds galactose but does not depurinate 28 S ribosomal RNA
journal, September 1989


Human Immunodeficiency Virus Protease Inhibitors
journal, June 1997