Self-regulating apoptosis of inflammatory cells owing to genotherapy

This invention relates to the therapeutic induction of apoptosis in activated inflammatory cells, or cells at a site of inflammation, by introducing into those cells a chimeric gene containing an apoptosis-inducing gene (AIG) driven by a promoter of an inducible gene activated in inflammation and a...

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Bibliographische Detailangaben
Hauptverfasser:	MARLIN STEVEN D, BARTON RANDALL W, TATAKE REVATI J
Format:	Patent
Sprache:	eng ; pol
Schlagworte:	BEER BIOCHEMISTRY CHEMISTRY COMPOSITIONS THEREOF CULTURE MEDIA DERIVATIVES THEREOF ENZYMOLOGY FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE HUMAN NECESSITIES HYGIENE MEDICAL OR VETERINARY SCIENCE METALLURGY MICROBIOLOGY MICROORGANISMS OR ENZYMES MUTATION OR GENETIC ENGINEERING NUCLEIC ACIDS NUCLEOSIDES NUCLEOTIDES ORGANIC CHEMISTRY PEPTIDES PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS SPIRITS SUGARS VINEGAR WINE
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Beschreibung
Zusammenfassung:	This invention relates to the therapeutic induction of apoptosis in activated inflammatory cells, or cells at a site of inflammation, by introducing into those cells a chimeric gene containing an apoptosis-inducing gene (AIG) driven by a promoter of an inducible gene activated in inflammation and a promoter enhancer such that the inflammatory cells are targeted. In one embodiment, the chimeric gene comprises at least one TNFalpha promoter enhancer attached to a functional copy of a minimal TNFalpha promoter and further attached to at least one copy of an apoptosis-inducing gene, wherein expression of the gene is driven by the TNFalpha promoter. Attachment can be direct, distal, proximal or combinations thereof. Example apoptosis-inducing genes include caspase 3, caspase 4, caspase 5, Granzyme B. Advantageously, the TNFp-AIG chimeric gene is expressed in only those cells producing the inflammatory cytokine, TNFalpha. In addition, the TNFp-AIG chimeric gene also sequesters inducible TNFp transcription factors, thereby reducing endogenous production of TNFalpha. The invention also relates to methods of making and using self-regulated apoptosis chimeric genes and pharmaceutical compositions containing them for treating inflammatory diseases.