Polynucleotides for Reducing Respiratory Syncytial Virus Gene Expression

Abstract

This invention pertains to polynucleotides, such as small interfering RNA (siRNA), useful for reducing the expression of respiratory syncytial virus (RSV) genes within a subject; and methods for treating a patient suffering from, or at risk of developing, an RSV infection by administering such polynucleotides to the subject.

1 : An isolated polynucleotide comprising a nucleic acid sequence targeted to a target nucleic acid sequence within a respiratory syncytial virus (RSV) gene or RSV transcript, wherein said polynucleotide inhibits expression of said RSV gene or transcript.  
     
     
         2 : The polynucleotide of  claim 1 , wherein said RSV is human RSV.  
     
     
         3 : The polynucleotide of  claim 1 , wherein said target nucleic acid sequence is at least a portion of the human RSV NS1 or NS2 gene or transcript.  
     
     
         4 : The polynucleotide of  claim 1 , wherein said target nucleic acid sequence is located in a region selected from the group consisting of the 5′ untranslated region (UTR), transcription start site, translation start site, and 3′ UTR.  
     
     
         5 : The polynucleotide of  claim 1 , wherein said polynucleotide is a small interfering RNA (siRNA).  
     
     
         6 : The polynucleotide of  claim 1 , wherein said polynucleotide is an antisense molecule.  
     
     
         7 : The polynucleotide of  claim 1 , wherein said polynucleotide is a ribozyme.  
     
     
         8 : The polynucleotide of  claim 1 , wherein said polynucleotide comprises SEQ ID NO:1 or SEQ ID NO:2.  
     
     
         9 : The polynucleotide of  claim 1 , wherein said RSV gene or RSV transcript is at least a portion of the bovine NS1 or NS2 gene or transcript.  
     
     
         10 : The polynucleotide of  claim 1 , wherein said polynucleotide further comprises a regulatory sequence operably linked to said nucleic acid sequence.  
     
     
         11 : The polynucleotide of  claim 10 , wherein said regulatory sequence is surfactant protein B, or a steroid response element, or both.  
     
     
         12 : A method for reducing the expression of a respiratory syncytial virus (RSV) gene in a subject, comprising administering a polynucleotide to the subject, wherein the polynucleotide comprises a nucleic acid sequence targeted to a target nucleic acid sequence within the RSV gene or an RSV transcript, and wherein the polynucleotide is administered in an effective amount to reduce expression of the RSV gene or transcript.  
     
     
         13 : The method of  claim 12 , wherein the subject is suffering from an RSV infection.  
     
     
         14 : The method of  claim 12 , wherein the subject is not suffering from an RSV infection.  
     
     
         15 : The method of  claim 12 , wherein the subject is human.  
     
     
         16 : The method of  claim 12 , wherein the subject is a non-human mammal.  
     
     
         17 : The method of  claim 12 , wherein the polynucleotide is administered such that the polynucleotide is delivered to cells within the subject selected from the group consisting of respiratory epithelial cells, dendritic cells, and monocytes.  
     
     
         18 : The method of  claim 12 , wherein the polynucleotide is administered to the subject intranasally.  
     
     
         19 : The method of  claim 12 , wherein the polynucleotide is administered intranasally as drops or as an aerosol.  
     
     
         20 : The method of  claim 12 , wherein said administering comprises administering a combination of polynucleotides that reduce the expression of both RSV NS1 and NS2 within the subject.  
     
     
         21 : The method of  claim 12 , wherein the polynucleotide is an siRNA and wherein the siRNA reduces expression of RSV NS1 and NS2 within the subject.  
     
     
         22 : The method of  claim 12 , wherein the RSV gene or transcript encodes a polypeptide that reduces production of type-I interferon by monocytes and dendritic cells within the subject.  
     
     
         23 : The method of  claim 12 , wherein the polynucleotide is administered to the subject as a nanoparticle.  
     
     
         24 : The method of  claim 12 , wherein the polynucleotide further comprises an operably linked promoter.  
     
     
         25 : The method of  claim 12 , wherein the polynucleotide further comprises an operably linked regulatory sequence, wherein the regulatory sequence is surfactant protein B, a steroid response element, or both.  
     
     
         26 : The method of  claim 12 , wherein the polynucleotide is administered in an amount effective to increase type I interferon within the subject.  
     
     
         27 : A vector comprising a nucleic acid sequence targeted to a target nucleic acid sequence within a respiratory syncytial virus (RSV) gene or RSV transcript; and an operably linked promoter.  
     
     
         28 : The vector of  claim 27 , wherein the vector is a viral vector.  
     
     
         29 : The vector of  claim 27 , wherein the vector is a non-viral vector.  
     
     
         30 : A composition comprising a polynucleotide comprising a nucleic acid sequence targeted to a target nucleic acid sequence within a respiratory syncytial virus (RSV) gene or RSV transcript; and a pharmaceutically acceptable carrier.  
     
     
         31 : The composition of  claim 30 , wherein said composition further comprises a vector carrying said polynucleotide.