Inducible nitric oxide synthase gene for treatment of disease
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsTimothy R. Billiar, Edith Tzeng, Andreas K. Nussler, David A. Geller, Richard L. Simmons
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Abstract
The present invention discloses a full-length human hepatocyte iNOS cDNA clone and various gene therapy applications utilizing an iNOS DNA sequence. In preferred embodiments of the disclosed invention, iNOS-directed gene therapy involves specific targeting of a DNA sequence encoding a protein or protein fragment with iNOS biological activity for treating vascular diseases and disorders, antitumor applications and in response to certain microbial infections.
Claims40
A method of treating a vascular occlusion within a mammalian host which comprises transferring an isolated nucleic acid polymer inserted into a viral or plasmid vector to a population of mammalian cells at the site of said occlusion, said nucleic acid polymer encoding a biologically active nitric oxide synthase which has the enzymatic activity of the iNOS of SEQ ID NO:2 such that said nucleic acid polymer is expressed in said cells to effect increased amounts of nitric oxide (NO) via iNOS catalysis in amounts and for a time sufficient to reduce said vascular occlusion.
A method of treating an occlusion of an arterial vessel which comprises:
- (a) clearing the site in said arterial vessel of occluding material;
- and
- (b) delivering an isolated nucleic acid polymer inserted into a viral or plasmid vector to a population of mammalian cells at the cleared occluded site in the arterial vessel, said nucleic acid polymer encoding a biologically active nitric oxide synthase which has the enzymatic activity of the iNOS of SEQ ID NO:2, such that said nucleic acid polymer is expressed in said cells at said cleared occluded site to effect an increased amount of nitric oxide (NO) via iNOS catalysis in amounts and for a time sufficient to attenuate vascular occlusion.
A method of treating a blood vessel occlusion which comprises:
- (a) forming a graft composed of a bypass vessel joined by proximal and distal anastomoses to bypass said occlusion;
- (b) isolating an anastomosis subsequent to graft suturing;
- and
- (c) delivering an isolated nucleic acid polymer inserted into a viral or plasmid vector to a population of mammalian cells at the site of said isolated anastomosis, said nucleic acid polymer encoding a biologically active nitric oxide synthase which has the enzymetic activity of the iNOS of SEQ ID NO:2, such that said nucleic acid polymer is expressed in said cells at said site to effect an increased amount of nitric oxide (NO) via iNOS catalysis in amounts and for a time sufficient to attenuate vascular occlusion.
Dependencies are inferred from the claim text.