Compositions, Methods, And Systems For Targeting And Destabilizing RNA Transcripts (OVAC)
AssigneeUTR Therapeutics Inc.
InventorChidiebere Awah
Life of this patent
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Abstract
The present disclosure encompasses molecules, including DNA and RNA molecules, for destabilizing mRNA transcripts, along with the preparation and use thereof. Specifically encompassed are methods for preparing these molecules, methods for utilizing these molecules in therapies, particularly cancer therapies, and vectors, host cells, and kits for these preparations and uses.
Claims20
A method of treating ovarian cancer in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising a plasmid vector comprising a therapeutically effective amount of a DNA molecule, wherein the DNA molecule comprises in the 5′ to 3′ direction of transcription relative to synthesis of a messenger RNA (mRNA) molecule comprising a 3′ UTR of an mRNA encoding a c-MYC protein:
- (a) a promoter, operatively linked to:
- (b) a nucleic acid sequence encoding a 3′ UTR of a c-MYC gene in the mRNA molecule in which one or more ARE poly(U) stabilizing motifs of the 3′ UTR of the mRNA are substituted with a nucleic acid sequence selected from CCUC, CUGC, ACCUC, AUUUU, UAAGUUAUG, UAACUUAU, UGCUGCCCU, GUAAAUAG, CCUCUGC, UCCUGCCCUC (SEQ ID NO:
- 50), CCUCGUAACUU (SEQ ID NO:
- 52), CCUCCUGCAUUU (SEQ ID NO:
- 54), UAAGUUAUCCUCUAUU (SEQ ID NO:
- 57), CUGCCUCUGCUAACUUAU (SEQ ID NO:
- 58), or CCUCCUGCCUC (SEQ ID NO:
- 53), and wherein the ovarian cancer is characterized by overexpression of c-MYC.
A method of treating a cancerous ovarian tumor in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising a plasmid vector comprising a therapeutically effective amount of a DNA molecule, wherein the DNA molecule comprises in the 5′ to 3′ direction of transcription relative to synthesis of a messenger RNA (mRNA) molecule comprising a 3′ UTR of an mRNA encoding a c-MYC protein:
- (a) a promoter, operatively linked to:
- (b) a nucleic acid sequence encoding a 3′ UTR of a c-MYC gene in the mRNA molecule in which one or more ARE poly(U) stabilizing motifs of the 3′ UTR of the mRNA are substituted with a nucleic acid sequence selected from CCUC, CUGC, ACCUC, AUUUU, UAAGUUAUG, UAACUUAU, UGCUGCCCU, GUAAAUAG, CCUCUGC, UCCUGCCCUC (SEQ ID NO:
- 50), CCUCGUAACUU (SEQ ID NO:
- 52), CCUCCUGCAUUU (SEQ ID NO:
- 54), UAAGUUAUCCUCUAUU (SEQ ID NO:
- 57), CUGCCUCUGCUAACUUAU (SEQ ID NO:
- 58), or CCUCCUGCCUC (SEQ ID NO:
- 53), wherein the tumor is characterized by overexpression of c-MYC, and wherein the tumor is metastatic.
A method of preventing metastasis of an cancerous ovarian tumor in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising a plasmid vector comprising a therapeutically effective amount of a DNA molecule, wherein the DNA molecule comprises in the 5′ to 3′ direction of transcription relative to synthesis of a messenger RNA (mRNA) molecule comprising a 3′ UTR of an mRNA encoding a c-MYC protein:
- (a) a promoter, operatively linked to:
- (b) a nucleic acid sequence encoding a 3′ UTR of a c-MYC gene in the mRNA molecule in which one or more ARE poly(U) stabilizing motifs of the 3′ UTR of the mRNA are substituted with a nucleic acid sequence selected from CCUC, CUGC, ACCUC, AUUUU, UAAGUUAUG, UAACUUAU, UGCUGCCCU, GUAAAUAG, CCUCUGC, UCCUGCCCUC (SEQ ID NO:
- 50), CCUCGUAACUU (SEQ ID NO:
- 52), CCUCCUGCAUUU (SEQ ID NO:
- 54), UAAGUUAUCCUCUAUU (SEQ ID NO:
- 57), CUGCCUCUGCUAACUUAU (SEQ ID NO:
- 58), or CCUCCUGCCUC (SEQ ID NO:
- 53), and wherein the tumor is characterized by overexpression of c-MYC.
A method of treating ovarian cancer in a subject having cancer progression after chemotherapy treatment, the method comprising administering to the subject a pharmaceutical composition comprising a plasmid vector comprising a therapeutically effective amount of a DNA molecule, wherein the DNA molecule comprises in the 5′ to 3′ direction of transcription relative to synthesis of a messenger RNA (mRNA) molecule comprising a 3′ UTR of an mRNA encoding a c-MYC protein:
- (a) a promoter, operatively linked to:
- (b) a nucleic acid sequence encoding a 3′ UTR of a c-MYC gene in the mRNA molecule in which one or more ARE poly(U) stabilizing motifs of the 3′ UTR of the mRNA are substituted with a nucleic acid sequence selected from CCUC, CUGC, ACCUC, AUUUU, UAAGUUAUG, UAACUUAU, UGCUGCCCU, GUAAAUAG, CCUCUGC, UCCUGCCCUC (SEQ ID NO:
- 50), CCUCGUAACUU (SEQ ID NO:
- 52), CCUCCUGCAUUU (SEQ ID NO:
- 54), UAAGUUAUCCUCUAUU (SEQ ID NO:
- 57), CUGCCUCUGCUAACUUAU (SEQ ID NO:
- 58), or CCUCCUGCCUC (SEQ ID NO:
- 53), and wherein the ovarian cancer is characterized by overexpression of c-MYC.
Dependencies are inferred from the claim text.