siRNA/Nanoparticle Formulations for Treatment of Middle-East Respiratory Syndrome Coronaviral Infection

Abstract

The present invention relates to compositions and methods for siRNA therapeutics for prevention and treatment of Middle East Respiratory Syndrome Corona Virus (MERS-CoA) 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 one or more conserved regions of the genome of a Middle-East Respiratory Syndrome Corona Virus (MERS-CoV) and a pharmaceutically acceptable carrier comprising a polymeric nanoparticle or a liposomal nanoparticle. 
     
     
         2 . The composition of  claim 1 , wherein the gene sequences in the conserved regions of the MERS-CoV are critical for the viral infection of a mammal. 
     
     
         3 . (canceled) 
     
     
         4 . The composition of  claim 1 , wherein the targeted conserved regions of the genome comprise gene sequences coding for MERS-CoV proteins selected from the group consisting of Papain-like protease (PL Pro ), RNA-dependent RNA polymerase (RdRp), and Spike protein. 
     
     
         5 - 7 . (canceled) 
     
     
         8 . The composition of  claim 4 , wherein the siRNA molecules are selected from the group consisting of SEQ ID NOs:1-18. 
     
     
         9 - 17 . (canceled) 
     
     
         18 . The composition of  claim 1 , wherein the polymeric nanoparticle carrier comprises a Histidine-Lysine co-polymer (HKP). 
     
     
         19 . (canceled) 
     
     
         20 . The composition of  claim 1 , wherein the liposomal nanoparticle carrier comprises a Spermine-Lipid Conjugate (SLiC) and cholesterol. 
     
     
         21 - 28 . (canceled) 
     
     
         29 . 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 . 
     
     
         30 - 36 . (canceled) 
     
     
         37 . The method of  claim 29 , wherein the mammal is a human. 
     
     
         38 . An siRNA molecule that targets a conserved region of the genome of a MERS-CoV. 
     
     
         39 . The siRNA molecule of  claim 38 , wherein the targeted conserved region of the genome comprises gene sequences coding for MERS-CoV proteins selected from the group consisting of Papain-like protease (PL Pro ), RNA-dependent RNA polymerase (RdRp), and Spike protein. 
     
     
         40 - 42 . (canceled) 
     
     
         43 . The siRNA molecule of  claim 38 , wherein the molecule is selected from the group consisting of the molecules identified in Table 3. 
     
     
         44 . The siRNA molecule of  claim 38 , wherein the wherein the siRNA molecules are selected from the group consisting of SEQ ID NOs:1-18. 
     
     
         45 - 47 . (canceled) 
     
     
         48 . A composition comprising the siRNA molecule of  claim 38  and a pharmaceutically acceptable carrier comprising a polymeric nanoparticle or a liposomal nanoparticle. 
     
     
         49 . A method of treating a mammal with a MERS infection comprising administering to said mammal a pharmaceutically effective amount of the composition of  claim 48 . 
     
     
         50 . The method of  claim 49 , wherein the subject mammal is a human. 
     
     
         51 . The composition of  claim 44 , wherein the siRNA molecules comprise derivatives of the identified siRNA molecules, the derivatives having 17-24 contiguous base pairs of original 25 contiguous base pairs of the identified molecules or one or more base pairs in addition to the original 25 contiguous base pairs of the identified molecules.