Inhibition of cellular proliferation by oligonucleotide binding to a chromosomal binding site for p53 protein
AssigneeAlton Ochsner Medical Foundation
InventorsRichard Re, Julia Cook
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Abstract
The present invention provides methods for inhibiting cell growth by providing a growing cell with an oligonucleotide capable of binding to a chromosomal binding site for p53 protein. Moreover, in a preferred embodiment these methods can be used for preventing and treating cancer.
Claims32
A method for inhibiting the growth of a cancerous mammalian cell, wherein said cell comprises a mutant p53 protein or lacks p53 protein, comprising providing said mammalian cell with a cell growth-inhibiting amount of a DNA oligonucleotide which binds to a chromosomal binding site of wild type p53 protein to form a complex between said oligonucleotide and said binding site, wherein said complex is sufficiently stable to inhibit said mammalian cell growth;
- and wherein said chromosomal binding site comprises any one of positions 60-83, 70-95, 71-82, 100-121 or 60-121 of SEQ ID NO:
- 1.
A method for treating cancer caused by a mutation or loss of a p53 gene which comprises administering to a patient a therapeutically effective amount of a DNA oligonucleotide which binds to a chromosomal binding site for a wild type p53 protein to form a complex between said oligonucleotide and said binding site, wherein said complex is sufficiently stable to inhibit cell growth;
- and wherein said chromosomal binding site comprises any one of position 60-83, 70-95, 71-82 or 100-121 of SEQ ID NO:
- 1.
A method for inhibiting chromosomal replication in a mammalian cell wherein said cell comprises a mutant p53 protein or lacks p53 protein, comprising providing a mammalian cell with a DNA replication-inhibiting amount of a DNA oligonucleotide which binds to a chromosomal binding site for wild type p53 protein to form a complex between said oligonucleotide and said binding site, wherein said complex is sufficiently stable to inhibit chromosomal replication;
- and wherein said chromosomal binding site comprises positions 60-83, 70-95, 71-82, 100-121 or 60-121 of SEQ ID NO:
- 1.
A composition comprising a therapeutically effective amount of an oligonucleotide comprising any one of SEQ ID NO:
- 8, SEQ ID NO:
- 9 or SEQ ID NO:
- 12 and a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.