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Title: 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:
Idaho National Laboratory (INL), Idaho Falls, ID (United States); BECHTEL BWXT IDAHO LLC
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)

Primary Structure of Three Distinct Isoabrins Determined by cDNA Sequencing journal January 1993
Ricin: structure, mode of action, and some current applications. journal February 1994
Cloning and expression of three abrin A-chains and their mutants derived by site-specific mutagenesisin Escherichia coli journal January 1994
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
T-immunogenic peptides are constituted of rare sequence patterns. Use in the identification of T epitopes in the human immunodeficiency virus gag protein journal October 1988
Increasing cytostatic effects of ricin A chain and Staphylococcus aureus enterotoxin A through in vitro hydrophobization with fatty acid residues journal February 1990
Poxvirus pathogenesis. journal January 1991
Recombinant proricin binds galactose but does not depurinate 28 S ribosomal RNA journal September 1989
Genomic cloning and characterization of a ricin gene from Ricinus Communis journal January 1985
Regulation of Intracellular Human Immunodeficiency Virus Type-1 Protease Activity journal April 1998
Preparation and characterization of recombinant proricin containing an alternative protease-sensitive linker sequence journal September 1992
Uptake of injected 125I-ricin by rat liver in vivo. Subcellular distribution and characterization of the internalized ligand journal May 1992
A microchemical facility for the analysis and synthesis of genes and proteins journal July 1984
Rationale for the Use of Immunotoxins in the Treatment of HIV-infected Humans journal January 1998
Crystal structure of the principal neutralization site of HIV-1 journal April 1994
Selective elimination of HIV-1-infected cells with an interleukin-2 receptor-specific cytotoxin journal June 1991