RNAi Modulation Of RSV And Therapeutic Uses Thereof

Abstract

The present invention is based on the in vivo demonstration that RSV can be inhibited through intranasal administration of iRNA agents as well as by parenteral administration of such agents. Further, it is shown that effective viral reduction can be achieved with more than one virus being treated concurrently. Based on these findings, the present invention provides general and specific compositions and methods that are useful in reducing RSV mRNA levels, RSV protein levels and viral titers in a subject, e.g., a mammal, such as a human. These findings can be applied to other respiratory viruses.

1 . A method of reducing the levels of a viral protein, viral mRNA or viral titer in a cell in a subject comprising the step of administering an iRNA agent to said subject, wherein the iRNA agent comprising a sense strand having at least 15 or more contiguous nucleotides complementary to gene from a first mammalian respiratory virus and an antisense strand having at least 15 or more contiguous nucleotides complementary to said sense strand, wherein said gene is selected from the group consisting of the P N or L gene of RSV. 
     
     
         2 . The method of  claim 1  wherein said agent comprises 15 or more nucleotides selected from one of the agents of Table 1 (a-c). 
     
     
         3 . The method of  claim 1 , wherein said the iRNA agent is administered intranasally to a subject. 
     
     
         4 . The method of  claim 1 , wherein said the iRNA agent is administered via inhalation or nebulization to a subject. 
     
     
         5 . The method of  claim 1 , wherein said the iRNA agent reduces the viral titer in said subject. 
     
     
         6 . The method of  claim 1  further comprising co-administering a second iRNA agent to said subject, wherein said second iRNA agent comprising a sense strand having at least 15 or more contiguous nucleotides complementary to second gene from said respiratory virus and an antisense strand having at least 15 or more contiguous nucleotides complementary to said sense strand. 
     
     
         7 . The method of  claim 6  wherein said agent comprises 15 or more nucleotides selected from one of the agents of Table 1 (a-c). 
     
     
         8 . The method of  claim 6 , wherein the subject is diagnosed as having a viral infection with said first and said second mammalian respiratory virus. 
     
     
         9 . A method of reducing the levels of a viral protein from a first and a second gene of a respiratory virus in a cell in a subject comprising the step of co-administering a first and a second iRNA agent to said subject, wherein said first iRNA agent comprising a sense strand having at least 15 or more contiguous nucleotides complementary to a first gene from a mammalian respiratory virus and an antisense strand having at least 15 or more contiguous nucleotides complementary to said sense strand and said second iRNA agent comprising a sense strand having at least 15 or more contiguous nucleotides complementary to a second gene from said mammalian respiratory virus and an antisense strand having at least 15 or more contiguous nucleotides complementary to said sense strand. 
     
     
         10 . The method of  claim 9  wherein said agents comprises 15 or more nucleotides selected from one of the agents of Table 1 (a-c).