MYC NUCLEIC ACIDS AND USES THEREOF
Disclosed herein are molecules and pharmaceutical compositions that mediate RNA interference against MYC. Also described herein include methods for treating a disease or disorder that comprises a molecule or a pharmaceutical composition that mediate RNA interference against MYC.
1 . A small interfering RNA (siRNA) molecule comprising a double-stranded polynucleotide molecule selected from
the duplex consisting of
(SEQ ID NO: 1)
AGGAACUAUGACCUCGACUdTsdT;
(SEQ ID NO: 2)
AGUCGAGGUCAUAGUUCCUdTsdT
the duplex consisting of
(SEQ ID NO: 5)
AAGAUGAGGAAGAAAUCGAdTsdT
and
(SEQ ID NO: 6)
UCGAUUUCUUCCUCAUCUUdTsdT;
the duplex consisting of
(SEQ ID NO: 7)
AGGAAGAAAUCGAUGUUGUdTsdT
and
(SEQ ID NO: 8)
ACAACAUCGAUUUCUUCCUdTsdT;
and
the duplex consisting of
(SEQ ID NO: 9)
AGCGCCCUGCGUGdTsdT
and
(SEQ ID NO: 10)
CACGCAGGGCAAAAAAGCUdTsdT;
wherein dT is the deoxy-thymidine residue and s is a phosphorothioate backbone modification; and
wherein the siRNA molecule downregulates the expression of MYC.
2 . The siRNA molecule of claim 1 , wherein the siRNA molecule comprises at least one 2′ modified nucleotide, at least one 2′-fluoro modified nucleotide, or at least one inverted abasic moiety.
3 . The siRNA molecule of claim 2 , wherein the 2′ modified nucleotide comprises 2′-O-methyl, 2′-O-methoxyethyl (2′-O-MOE), 2′-O-aminopropyl, 2′-deoxy, 2′-deoxy-2′-fluoro, 2′-O-aminopropyl (2′-O-AP), 2′-O-dimethylaminoethyl (2′-O-DMAOE), 2′-O-dimethylaminopropyl (2′-O-DMAP), 2′-O-dimethylaminoethyloxyethyl (2′-O-DMAEOE), or 2′-O-N-methylacetamido (2′-O-NMA) modified nucleotide.
4 . The siRNA molecule of claim 2 , wherein the 2′ modified nucleotide comprises a locked nucleic acid (LNA) or an ethylene nucleic acid (ENA).
5 . A pharmaceutical composition comprising:
a) the siRNA molecule of claim 1 ; and
b) a pharmaceutically acceptable excipient.
6 . The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is formulated as a nanoparticle formulation.
7 . The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is formulated for parenteral, oral, intranasal, buccal, rectal, or transdermal administration.
8 . A method of treating cancer in a patient in need thereof, comprising administering to the said patient a composition comprising the siRNA molecule of claim 1 .
9 . The method of claim 8 , wherein the cancer comprises a MYC-associated cancer.