Cloning, overexpression and therapeutic use of bioactive histidine ammonia lyase
AssigneeUniversity of South Carolina
InventorsJoseph Roberts, Natarajan Sethuraman, Thomas MacAllister
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Abstract
Histidine ammonia lyase (HAL) isolated from Corynebacteriaceae can decrease serum histidine levels, induce accumulation of urocanic acid, and is not inhibited by L-histidinol. As a result, histidine ammonia lyases similar to the one isolated from Corynebacteriaceae are uniquely suitable for combination therapy with L-histidinol to treat histidine- and/or histamine-dependent pathologies, for example, infectious viruses, such as human Respiratory Syncytial Virus (RSV), Herpes Simplex Virus (HSV), and Human Immunodeficiency Virus (HIV), as well as cancers.
Claims21
A method of treating a viral infection, comprising administering to a patient suffering from the viral infection a therapeutic amount of a polypeptide having histidine ammonia lyase activity.
A method for treating a patient suffering from a cancer, comprising administering to the patient suffering from said cancer a therapeutic amount of a polypeptide having about 40 IU/mg protein of histidine ammonia lyase activity, wherein said histidine ammonia lyase activity is not substantially decreased in the presence of L-histidinol or a therapeutic salt thereof and the polypeptide corresponds in sequence to histidine ammonia lyase of Corynebacteriaceae, and a therapeutic amount of L-histidinol or a therapeutic salt thereof.
A method for reducing toxicity to normal cells from chemotherapeutic agents, comprising
- (i) administering to a patient a therapeutically effective amount of a polypeptide having histidine ammonia lyase activity, and
- (ii) additionally administering to said patient a therapeutically effective amount of a chemotherapeutic agent, whereby said polypeptide having histidine ammonia lyase activity selectively depletes circulating histidine and causes growth arrest in normal cells, without affecting the growth of tumor cells.
A method for delivering an immunosuppressant to a patient, comprising:
- administering to a patient a therapeutically effective amount of a polypeptide having histidine ammonia lyase activity, wherein said polypeptide is PEGylated and wherein said polypeptide generates trans-urocanic acid (t-UA) in vivo;
- and subjecting the patient to an irradiating agent, wherein said irradiating agent causes the photoisomerization of t-UA to its cis isomer (c-UA), and wherein said cis isomer comprises an immunosuppressive property.
A method of treating a viral infection comprising administering to a patient suffering from the viral infection a therapeutic amount of a histidine analog and a polypeptide having histidine ammonia lyase activity.
Dependencies are inferred from the claim text.