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Title: Selective destruction of cells infected with human immunodeficiency virus

Patent ·
OSTI ID:1174512

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.

Research Organization:
Idaho National Laboratory (INL), Idaho Falls, ID (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
AC07-94ID13223
Assignee:
Bechtel BWXT Idaho, LLC (Idaho Falls, ID)
Patent Number(s):
6,627,197
Application Number:
09/785,921
OSTI ID:
1174512
Country of Publication:
United States
Language:
English

References (7)

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

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