Anti-viral guanosine-rich oligonucleotides
AssigneeAronex Pharmaceuticals, Inc.
InventorsRobert F. Rando, Susan Fennewald, Joseph G. Zendegui, Joshua O. Oiwana, Michael E. Hogan
Life of this patent
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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.
Claims22
An oligonucleotide containing at least about 40% guanosine residues and at least two runs of at least two guanosine nucleotides selected from the group consisting of SEQ ID NOS 2-27, 29 and 31-39;
- optionally modified at the 3′ terminus by attachment of a substituent moiety selected from the group consisting of propylamine, polyamine, poly-L-lysine and cholesterol;
- optionally modified at the 5′-terminus by attachment of a substituent moiety selected from the group consisting of propylamine, polyamine, poly-L-lysine and cholesterol;
- and
- optionally modified by replacement of at least one phosphodiester moiety with a phosphorothioate moiety.
An oligonucleotide containing at least about 40% guanosine residues and at least two runs of at least two guanosine nucleotides selected from the group consisting of SEQ ID NOS 46-52;
- optionally modified at the 3′ terminus by attachment of a substituent moiety selected from the group consisting of propylamine, polyamine, poly-L-lysine and cholesterol;
- optionally modified at the 5′-terminus by attachment of a substituent moiety selected from the group consisting of propylamine, polyamine, poly-L-lysine and cholesterol;
- and
- optionally modified by replacement of at least one phosphodiester moiety with a phosphorothioate moiety.
An oligonucleotide comprising at least about 40% guanosine nucleotides and at least two runs of at least two guanosine nucleotides selected from the group consisting of SEQ ID NOS 2-27, 29, 31-39 and 46-52, said oligonucleotide further comprising a chemical modification at the 3′ terminus with a moiety selected from the group consisting of propylamine, polyamine, poly-L-lysine and cholesterol.
An oligonucleotide comprising at least about 40% guanosine nucleotides and at least two runs of at least two guanosine nucleotides selected from the group consisting of SEQ ID NOS 2-27, 29, 31-39 and 46-52, said oligonucleotide further comprising a chemical modification at the 5′ terminus with a moiety selected from the group consisting of propylamine, polyamine, poly-L-lysine and cholesterol.
An oligonucleotide comprising at least about 40% guanosine nucleotides and at least two runs of at least two guanosine nucleotides selected from the group consisting of SEQ ID NOS 2-27, 29, 31-39 and 46-52, said oligonucleotide further comprising at least one phosphorothioate linkage.
An oligonucleotide selected from the group consisting of SEQ ID NOS 2-27, 29 and 31-39.
An oligonucleotide selected from the group consisting of SEQ ID NOS 46-52.
An oligonucleotide having the sequence of any one oligonucleotide defined in claim or 16, oligonucleotide containing a chemical modification at the 5′ terminus with a moiety selected from the group consisting of propylamine, polyamine, poly-L-lysine and cholesterol.
Dependencies are inferred from the claim text.