Abstract: A method and compositions for treating viral infection (IV) vitro and in vivo using a guanosine-rich oligonucleotide. The oligonucleotides have sufficient guanosine to form a guanosine tetrad. Also provided are oligonucleotides of at least two runs of at least two guanosines. Also provided are guanosine-rich oligonucleotides and methods for treating viral infections in humans, and a method for designing guanosine-rich oligonucleotides having anti-viral activity and integrase inhibition activity.
Type:
Grant
Filed:
October 28, 1999
Date of Patent:
March 12, 2002
Assignee:
Aronex Pharmaceuticals, Inc.
Inventors:
Robert F. Rando, Susan Fennewald, Joseph G. Zendegui, Joshua O. Ojwang, Michael E. Hogan, Yves Pommier, Abhijit Mazumder
Abstract: A recombinant adenoviral vector encoding the human tissue factor pathway inhibitor (TFPI) gene is disclosed which is useful for transduction of vascular smooth muscle cells at a selected blood vessel site to provide local vascular expression of TFPI. A method of using the transduced hTFPI cDNA as an in vivo antithrombotic agent to provide localized production of hTFPI for protecting an at-risk site against thrombus deposition is also disclosed. Gene therapy using the new TFPI expression vector is also expected to deter the development of chronic vascular stenosis in blood vessels (arteries, veins, arteriovenous shunts, and endovascular grafts) and deterring intimal hyperplasia.
Abstract: Methods for induction of E2F-1 related vascular smooth muscle cell (VSMC) death to limit vascular stenosis or restenosis, to regress atherosclerotic plaque and to prevent atherogenesis are disclosed. Also disclosed is an adenovirus vector containing the E2F-1 gene, and a method of transferring the gene to a vessel or graft. A method of limiting cell proliferation and/or reducing cell numbers includes transferring the E2F-1 gene into VSMC to achieve overexpression of E2F-1 gene product, which drives vascular cells into S-phase and thereby causes their subsequent death.
Abstract: The oligonucleotides have sufficient guanosine to form a guanosine tetrad and can be composed of at least about 40% guanosine nucleotides, the nucleotide sequence containing at least two runs of at least two guanosines. Some of the new oligonucleotides also contain phosphorothioate backbones and 3′ end modifications. Representative guanosine-rich oligonucleotides of the present invention demonstrate anti-viral activity in tissue culture against HSV-2, HIV-1, HCMV and FMLV, and show specific inhibition of bacterial RNA polymerase enzymes T7 and T3, the FMLV and HIV-1 reverse transcriptase enzyme and eukaryotic RNA polymerase.
Type:
Grant
Filed:
October 23, 1995
Date of Patent:
February 6, 2001
Assignee:
Aronex Pharmaceuticals, Inc.
Inventors:
Robert F. Rando, Susan Fennewald, Joseph G. Zendegui, Joshua O. Oiwana, Michael E. Hogan