Treatment of disease conditions via administration of DNA repair enzyme
AssigneeUniversity of South Alabama
InventorsGlenn Wilson, Susan Ledoux, Mikhail Alexeyev, Inna Shokolenko, Mark N. Gillespie
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Abstract
The present invention is directed to compositions and methods of preserving viability of islets of Langerhans for transplantation, and treating various diseases and other abnormal or pathological conditions, including inflammatory bowel disease, ischemic heart disease, acute lung injury, acute respiratory distress syndrome and radiation-induced brain injury, with DNA repair enzymes that are directed to the mitochondria.
Claims28
A method of enhancing viability of islets of Langerhans which comprise β-cells for purposes of transplantation, comprising contacting the islets of Langerhans with a composition comprising a multi-domain conjugate comprising, from N-terminus to C-terminus, a mitochondrial localization sequence comprising a manganese Superoxide Dismutase (MNSOD) sequence MLSRAVCGTSRQLAPALGYLGSRQ (SEQ ID NO:1), a DNA repair enzyme comprising human 8-oxoguanine DNA glycosylase (hOGG1) or Endonuclease III (Endo III), and a protein transduction domain comprising a TAT protein having the amino acid sequence YGRKKRRQRRR (SEQ ID NO:8), in an amount effective to enhance viability of the β-cells.
A method of treating oxidative-stress induced damage to mitochondrial DNA, comprising administering to a patient in need thereof, a composition comprising a multi-domain conjugate or fusion protein comprising, from N-terminus to C-terminus, a mitochondrial localization sequence comprising a manganese Superoxide Dismutase (MNSOD) sequence MLSRAVCGTSRQLAPALGYLGSRQ (SEQ ID NO:1), a DNA repair enzyme comprising human 8-oxoguanine DNA glycosylase (hOGG1) or Endo III, and a protein transduction domain comprising a TAT protein having the amino acid sequence YGRKKRRQRRR (SEQ ID NO:8), in a therapeutically effective amount.
A composition comprising a culture of islets of Langerhans which comprise β-cells and a multi-domain conjugate comprising, from N-terminus to C-terminus, a mitochondrial localization sequence comprising a manganese Superoxide Dismutase (MNSOD) sequence MLSRAVCGTSRQLAPALGYLGSRQ (SEQ ID NO:1), a DNA repair enzyme comprising human 8-oxoguanine DNA glycosylase (hOGG1) or Endo III, and a protein transduction domain comprising a TAT protein having the amino acid sequence YGRKKRRQRRR (SEQ ID NO:8), in an amount effective to enhance viability of the β-cells.
A composition for inhibiting damage to mitochondrial DNA, comprising a multi-domain conjugate or fusion protein comprising, from N-terminus to C-terminus, a mitochondrial targeting sequence comprising a manganese Superoxide Dismutase (MNSOD) sequence MLSRAVCGTSRQLAPALGYLGSRQ (SEQ ID NO:1), a DNA repair enzyme comprising human 8-oxoguanine DNA glycosylase (hOGG1) or Endo III, and a protein transduction domain comprising a TAT protein having the amino acid sequence YGRKKRRQRRR (SEQ ID NO:8), in a therapeutically effective amount, and a pharmaceutically acceptable carrier.
A fusion protein, comprising, from N-terminus to C-terminus, a mitochondrial targeting sequence comprising a manganese Superoxide Dismutase (MNSOD) sequence MLSRAVCGTSRQLAPALGYLGSRQ (SEQ ID NO:1), a DNA repair enzyme comprising human 8-oxoguanine DNA glycosylase (hOGG1), and a protein transduction domain comprising a TAT protein having the amino acid sequence YGRKKRRQRRR (SEQ ID NO:8).
A fusion protein, comprising, from N-terminus to C-terminus, a mitochondrial targeting sequence comprising a manganese Superoxide Dismutase (MNSOD) sequence MLSRAVCGTSRQLAPALGYLGSRQ (SEQ ID NO:1), a DNA repair enzyme comprising Endo III, and a protein transduction domain comprising a TAT protein having the amino acid sequence YGRKKRRQRRR (SEQ ID NO:8).
Dependencies are inferred from the claim text.