Fas/FasL or other death receptor targeted methods and compositions for killing tumor cells
AssigneePromising Future, LLC
InventorsCarol Kruse, Richard Tritz
Life of this patent
Estimating the term…
Abstract
Provided herein are methods and compositions for killing tumor cells. In certain embodiments, compositions can promote apoptosis by down-regulating FAPP2 and PATZ1 products.
Claims22
A method for inhibiting proliferation of brain tumor cells, which comprises:
- administering to brain tumor cells a siNA agent that reduces the amount of RNA encoding a Fas/FasL apoptosis gating polypeptide in an amount sufficient to inhibit proliferation of the brain tumor cells,
- wherein the Fas/FasL apoptosis gating polypeptide is a FAPP2 polypeptide or a PATZ1 polypeptide, and
- wherein the siNA agent comprises one or more of the nucleotide sequences:
- (SEQ ID NO:
- 26)
- 5′-GAUGGAUCUUGUUGGAAAUUU-3′
- (SEQ ID NO:
- 27)
- 5′-AUUUCCAACAAGAUCCAUCUU-3′
- (SEQ ID NO:
- 28)
- 5′-GAUGGAUCUUGUUGGAAAUUsU-3′
- (SEQ ID NO:
- 29)
- 5′-AUUUCCAACAAGAUCCAUCUsU-3′
- (SEQ ID NO:
- 30)
- 5′-GAuGGAucuuGuuGGAAAuusu-3′
- (SEQ ID NO:
- 31)
- 5′-AUUUCcAACAAGAUCcAUCUsU-3′
- (SEQ ID NO:
- 32)
- 5′-GUCUAUGGAAGAAAUAGUUUU-3′
- (SEQ ID NO:
- 33)
- 5′-UUACUACUACUACUACUACUU-3′
- (SEQ ID NO:
- 34)
- 5′-GUCUAUGGAAGAAAUAGUUUsU-3′
- (SEQ ID NO:
- 35)
- 5′-UUACUACUACUACUACUACUsU-3′
- (SEQ ID NO:
- 36)
- 5′-GucuAuGGAAGAAAuAGuuusU-3′
- (SEQ ID NO:
- 37)
- 5′-UuACuACuACuACuACuACUsU-3′
- wherein s is a phosphorothioate linkage and lowercase nucleotide designations designate a nucleotide having a 2′-O-methyl modification.
A method for treating a brain tumor in a subject, which comprises:
- administering to a subject in need thereof a siNA agent that reduces the amount of RNA encoding a FAPP2 polypeptide or a PATZ1 polypeptide in an amount sufficient to inhibit proliferation of cells in the brain tumor in the subject,
- wherein the siNA agent comprises comprises one or more of the nucleotide sequences:
- (SEQ ID NO:
- 26)
- 5′-GAUGGAUCUUGUUGGAAAUUU-3′
- (SEQ ID NO:
- 27)
- 5′-AUUUCCAACAAGAUCCAUCUU-3′
- (SEQ ID NO:
- 28)
- 5′-GAUGGAUCUUGUUGGAAAUUsU-3′
- (SEQ ID NO:
- 29)
- 5′-AUUUCCAACAAGAUCCAUCUsU-3′
- (SEQ ID NO:
- 30)
- 5′-GAuGGAucuuGuuGGAAAuusu-3′
- (SEQ ID NO:
- 31)
- 5′-AUUUCcAACAAGAUCcAUCUsU-3′
- (SEQ ID NO:
- 32)
- 5′-GUCUAUGGAAGAAAUAGUUUU-3′
- (SEQ ID NO:
- 33)
- 5′-UUACUACUACUACUACUACUU-3′
- (SEQ ID NO:
- 34)
- 5′-GUCUAUGGAAGAAAUAGUUUsU-3′
- (SEQ ID NO:
- 35)
- 5′-UUACUACUACUACUACUACUsU-3′
- (SEQ ID NO:
- 36)
- 5′-GucuAuGGAAGAAAuAGuuusU-3′
- (SEQ ID NO:
- 37)
- 5′-UuACuACuACuACuACuACUsU-3′
- wherein s is a phosphorothioate linkage and lowercase nucleotide designations designate a nucleotide having a 2′-O-methyl modification.
A method for treating a brain tumor in a subject, which comprises administering to a subject in need thereof a ribozyme that reduces the amount of RNA encoding a FAPP2 polypeptide or a PATZ1 polypeptide in an amount sufficient to inhibit proliferation of cells in the brain tumor in the subject,
- wherein the ribozyme comprises one or more of the nucleotide sequences:
- (SEQ ID NO:
- 26)
- 5′-GAUGGAUCUUGUUGGAAAUUU-3′
- (SEQ ID NO:
- 27)
- 5′-AUUUCCAACAAGAUCCAUCUU-3′
- (SEQ ID NO:
- 28)
- 5′-GAUGGAUCUUGUUGGAAAUUsU-3′
- (SEQ ID NO:
- 29)
- 5′-AUUUCCAACAAGAUCCAUCUsU-3′
- (SEQ ID NO:
- 30)
- 5′-GAuGGAucuuGuuGGAAAuusu-3′
- (SEQ ID NO:
- 31)
- 5′-AUUUCcAACAAGAUCcAUCUsU-3′
- (SEQ ID NO:
- 32)
- 5′-GUCUAUGGAAGAAAUAGUUUU-3′
- (SEQ ID NO:
- 33)
- 5′-UUACUACUACUACUACUACUU-3′
- (SEQ ID NO:
- 34)
- 5′-GUCUAUGGAAGAAAUAGUUUsU-3′
- (SEQ ID NO:
- 35)
- 5′-UUACUACUACUACUACUACUsU-3′
- (SEQ ID NO:
- 36)
- 5′-GucuAuGGAAGAAAuAGuuusU-3′
- (SEQ ID NO:
- 37)
- 5′-UuACuACuACuACuACuACUsU-3′
- wherein s is a phosphorothioate linkage and lowercase nucleotide designations designate a nucleotide having a 2′-O-methyl modification.
A composition comprising the nucleic acid:
- (SEQ ID NO:
- 1)
- 5′-NNNNNNNCUGAUGAGpdpdpdpdCGAANNNNNNNNN-3′
- wherein N indicates any of DNA bases A, C, G, T, or any of RNA bases A, C, G, U, or any of 2′-O-methylated RNA bases A, C, G, U,
- wherein A, C, G, indicate DNA bases A, C, G, or RNA bases A, C, G, or 2′ 0-methyl RNA bases A, C, G,
- wherein U indicates a RNA base U or 2′-O-methyl RNA base U, and
- wherein pd indicates propanediol linkage.
A composition comprising one or both of the following nucleic acids:
- (SEQ ID NO:
- 30)
- 5′-GAuGGAucuuGuuGGAAAuusu-3′
- (SEQ ID NO:
- 31)
- 5′-AUUUCcAACAAGAUCcAUCUsU-3′
- wherein s is a phosphorothioate linkage and lowercase nucleotide designations designate a nucleotide having a 2′-O-methyl modification.
A composition comprising one or both of the following nucleic acids:
- (SEQ ID NO:
- 36)
- 5′-GucuAuGGAAGAAAuAGuuusU-3′
- (SEQ ID NO:
- 37)
- 5′-UuACuACuACuACuACuACUsU-3′
- wherein s is a phosphorothioate linkage and lowercase nucleotide designations designate a nucleotide having a 2′-O-methyl modification.
Dependencies are inferred from the claim text.