Genetically modified manganese superoxide dismutase for treating oxidative damage
AssigneeThe Webb-Waring Institute for Biomedical Research
InventorsJoe M. McCord, Bifeng Gao, Sonia C. Flores
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Abstract
This invention discloses a genetically modified manganese superoxide dismutase nucleic acid molecule and protein. Also disclosed are recombinant molecules, recombinant cells, therapeutic compositions and methods of using the modified manganese superoxide dismutase to treat oxidative damage.
Claims23
An isolated mutant manganese superoxide dismutase protein comprising an enzymatically active portion of manganese superoxide dismutase (MnSOD) and a region which binds to polyanionic polysaccharides or proteoglycans on endothelial cell surfaces, wherein said protein is encoded by a nuclcleic acid molecule that hybridizes under conditions that achieve hyridization permitting 30% or less mismatch of nucleotides, to a nucleic acid molecule selected from the group consisting of a nucleic acid molecule comprising both nucleic acid sequences SEQ ID NO:1 and SEQ ID NO:4, a nucleic acid molecule comprising a nucleic acid sequences SEQ ID NO:6, and a nucleic acid molecule comprising a nucleic acid sequences SEQ ID NO:8, wherein said conditions comprise hybridizing in a soluition comprising 6×SSC or 6×SSPE at a temperature 20-25° C. below Tm, and washing at 12-20° C. below said Tm.
A therapeutic composition to protect a mammal from oxidative damage, comprising:
- a. a protective compound selected from the group consisting of:
- (i) an isolated mutant manganese superoxide dismutase (MnSOD) protein comprising an enzymatically active portion of MnSOD and a C-termial region which binds to polyanionic polysaccharides or proteoglycans on endothelial cell surfaces, wherein said protein is encoded by a nucleic acid molecule that hybridizes under conditions that achieve hybridization permitting 30% or less mismatch of nucleotides, to a nucleic acid molemule selected from the group consisting of a nucleic acid moleculc comprising both nucleic acid sequences SEQ ID NO:1 and SEQ ID NO:4, a nucleic acid molecule comprising a nucleic acid sequence SEQ ID NO:6, and a nucleic acid molecule comprising a nucleic acid sequence SEQ ID NO:8, wherein said conditions comprise hybridzing in a solution comprising 6×SSC or 6×SSPE at a temperature 20-25° C. below Tm, and washing at 12-20° C. below said Tm;
- and,
- (ii) an isolated nucleic acid molecule comprising a nucleic acid sequence encoding said isolated mutant manganese superoxide dismutase (MnSOD) protein of (a);
- and,
- b. a pharmaceutically acceptable delivery vehicle.
A method to protect a mammal from oxidativc damage, comprising administering to a mammal a mutant manganese superoxide dismutase (MnSOD) protein comprising an enzymatically active portion of MnSOD and a C-terminal region which binds to polyanionic polysaccharides or proteoglycans on endothelial cell surfaces, wherein said protein is encoed by a nucleic acid motecule that hybridizes under conditions that achieve hybridization permitting 30% or less mismatch of nucleotides, to a nucleic acid molecule seleted from the group connsisting of a nucleic acid molecule comprisin both nucleic acid sequences SEQ ID NO:1 and SEQ ID NO:4, a nucleic acid molecule comprising a nucleic acid seguerce SEQ ID NO:6, and a nucleic acid moleculc comprising nucleic acid sequence SEQ ID NO:8, wherein said condtions comprise hybridizing in a solution comprising 6×SSC or 6×SSPE at a temperature 20-25° C. below Tm, and washing at 12-20° C. below said Tm.
Dependencies are inferred from the claim text.