Sirna/nanoparticle formulations for treatment of middle-east respiratory syndrome coronaviral infection
The present invention relates to compositions and methods for siRNA therapeutics for prevention and treatment of Middle East Respiratory Syndrome Corona Virus (MERS-CoV) infections. The compositions include a pharmaceutical composition comprising siRNA cocktails that target viral genes and pharmaceutically acceptable polymeric nanoparticle carriers and liposomal nanoparticle carriers.
1. A pharmaceutical composition comprising at least two different siRNA molecules that target the MERS-CoV Spike protein, and a pharmaceutically acceptable carrier comprising a polymeric nanoparticle or a liposomal nanoparticle, wherein the siRNA molecules are selected from the group consisting of:
(SEQ ID NO: 12)
MSP1: GGCCGUACAUAUUCUAACAUAACUA,
(SEQ ID NO: 700)
MSP2: GCCGUACAUAUUCUAACAUAACUAU,
(SEQ ID NO: 13)
MSP3: CCGAAGAUGAGAUUUUAGAGUGGUU,
(SEQ ID NO: 14)
MSP4: CCCAGUUUAAUUAUAAACAGUCCUU,
(SEQ ID NO: 15)
MSP5: GGCUUCACUACAACUAAUGAAGCUU,
(SEQ ID NO: 16)
MSP6: CCCCUGUUAAUGGCUACUUUAUUAA,
(SEQ ID NO: 17)
MSP7: CCCUGUUAAUGGCUACUUUAUUAAA,
and
(SEQ ID NO: 18)
MSP8: GCCGCAUAAGGUUCAUGUUCACUAA.
2. A pharmaceutical composition comprising at least two different siRNA molecules that target the genome of a MERS-CoV, wherein a first siRNA molecule comprises MRR2:
GGGAUUUCAUGCUUAAAACAUUGUA (SEQ ID NO: 20) and a second siRNA molecule comprises MSP2: GCCGUACAUAUUCUAACAUAACUAU (SEQ ID NO: 700).
3. A pharmaceutical composition comprising a siRNA cocktail, MSTRS1, wherein a first siRNA molecule comprises MRR1:
CCCAGUGUUAUUGGUGUUUAUCAUA (SEQ ID NO: 21) and a second siRNA molecule comprises MSP1: GGCCGUACAUAUUCUAACAUAACUA (SEQ ID NO: 12) and a pharmaceutically acceptable carrier comprising a polymeric nanoparticle or a liposomal nanoparticle.
4. A pharmaceutical composition comprising a siRNA cocktail, MSTPRS1, wherein a first siRNA molecule comprises MPL1:
CGCAAUACGUAAAGCUAAAGAUAU (SEQ ID NO: 22), a second siRNA molecule comprises MRR1: CCCAGUGUUAUUGGUGUUUAUCAUA (SEQ ID NO: 7), and a third siRNA molecule comprises MSP1: GGCCGUACAUAUUCUAACAUAACUA (SEQ ID NO:12) and a pharmaceutically acceptable carrier comprising a polymeric nanoparticle or a liposomal nanoparticle.
5. The composition of claim 1 , wherein the polymeric nanoparticle carrier comprises a Histidine-Lysine co-polymer (HKP).
6. The composition of claim 1 , wherein the liposomal nanoparticle carrier comprises a Spermine-Lipid Conjugate (SLiC) and cholesterol.
7. A method of treating a mammal with a MERS infection comprising administering to said mammal a pharmaceutically effective amount of the composition of claim 1 .
8. The method of claim 7 , wherein the mammal is a human.
9. An siRNA molecule that targets a conserved region of the genome of a MERS-CoV wherein the molecule is selected from the group consisting of the molecules of SEQ ID NOs 12, 1031, 700, 1032, 703, 1033, 717, 1034, 13, 1035, 741, 1036, 14, 1037, 765, 1038, 770, 1039, 771, 1040, 774, 1041, 15, 1042, 16, 1043, 17, 1044, 813, 1045, 18, and 1046.
10. An siRNA molecule that targets a conserved region of the genome of a MERS-CoV selected from the group consisting of:
(SEQ ID NO: 12)
MSP1: GGCCGUACAUAUUCUAACAUAACUA,
(SEQ ID NO: 700)
MSP2: GCCGUACAUAUUCUAACAUAACUAU,
(SEQ ID NO: 13)
MSP3: CCGAAGAUGAGAUUUUAGAGUGGUU,
(SEQ ID NO: 14)
MSP4: CCCAGUUUAAUUAUAAACAGUCCUU,
(SEQ ID NO: 15)
MSP5: GGCUUCACUACAACUAAUGAAGCUU,
(SEQ ID NO: 16)
MSP6: CCCCUGUUAAUGGCUACUUUAUUAA,
(SEQ ID NO: 17)
MSP7: CCCUGUUAAUGGCUACUUUAUUAAA,
and
(SEQ ID NO: 18)
MSP8: GCCGCAUAAGGUUCAUGUUCACUAA.
11. A composition comprising the siRNA molecule of claim 9 and a pharmaceutically acceptable carrier comprising a polymeric nanoparticle or a liposomal nanoparticle.
12. A method of treating a mammal with a MERS infection comprising administering to said mammal a pharmaceutically effective amount of the composition of claim 11 .
13. The method of claim 12 , wherein the mammal is a human.
14. The composition of claim 2 , wherein if a polymeric nanoparticle carrier is present said carrier comprises a Histidine-Lysine co-polymer (HKP) and if a liposomal nanoparticle carrier is present said carrier comprises a Spermine-Lipid Conjugate (SLiC) and cholesterol.
15. The composition of claim 3 , wherein if a polymeric nanoparticle carrier is present said carrier comprises a Histidine-Lysine co-polymer (HKP) and if a liposomal nanoparticle carrier is present said carrier comprises a Spermine-Lipid Conjugate (SLiC) and cholesterol.
16. The composition of claim 4 , wherein if a polymeric nanoparticle carrier is present said carrier comprises a Histidine-Lysine co-polymer (HKP) and if a liposomal nanoparticle carrier is present said carrier comprises a Spermine-Lipid Conjugate (SLiC) and cholesterol.
17. A method of treating a mammal with a MERS infection comprising administering to said mammal a pharmaceutically effective amount of the composition of claim 2 .
18. A method of treating a mammal with a MERS infection comprising administering to said mammal a pharmaceutically effective amount of the composition of claim 3 .
19. A method of treating a mammal with a MERS infection comprising administering to said mammal a pharmaceutically effective amount of the composition of claim 4 .
20. A method of treating a mammal with a MERS infection comprising administering to said mammal a pharmaceutically effective amount of the composition of claim 10 .