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Selective Destruction Of Cells Infected With The Human Immunodeficiency Virus

Patent ·
OSTI ID:880117
Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a varient 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.
Research Organization:
LOCKHEED MARTIN IDAHO TECH CO; BECHTEL BWXT IDAHO LLC; Idaho National Laboratory (INL), Idaho Falls, ID (United States)
DOE Contract Number:
AC07-94ID13223; AC07-99ID13727; AC07-05ID14517
Assignee:
Battelle Energy Alliance, LLC (Idaho Falls, ID)
Patent Number(s):
US 7,018,633
Application Number:
10/618560
OSTI ID:
880117
Country of Publication:
United States
Language:
English

References (17)

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Preparation and characterization of recombinant proricin containing an alternative protease-sensitive linker sequence journal September 1992
Selective elimination of HIV-1-infected cells with an interleukin-2 receptor-specific cytotoxin journal June 1991
Uptake of injected 125I-ricin by rat liver in vivo. Subcellular distribution and characterization of the internalized ligand journal May 1992

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