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.
Claims23
An isolated polypeptide having histidine ammonia lyase activity, wherein said histidine ammonia lyase activity is not substantially decreased in the presence of a histidine analog.
A method of treatment, comprising administering to a patient suffering from a viral infection a therapeutic amount of a polypeptide having histidine ammonia lyase activity.
A method for treating disease, comprising administering to a patient a therapeutically effective amount of a polypeptide having histidine ammonia lyase activity, and administering to said patient a therapeutically effective amount of a chemotherapeutic agent or a retroviral vector.
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 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.
An isolated DNA sequence comprising SEQ ID NO:
- 7.
Dependencies are inferred from the claim text.