Methods and compositions for prevention or treatment of rsv infection

Abstract

Methods and compositions are provided for the prevention or treatment of RSV infection in a human. The methods include administering one or more doses of a composition comprising an siRNA. The dose can be formulated for topical or parenteral administration. Topical administration includes administration as a nasal spray, or by inhalation of respirable particles or droplets. The siRNA comprises a sense strand of ALN-RSV01 and an antisense strand of ALN-RSV01.

1 . An siRNA composition comprising a therapeutically effective amount of ALN-RSV01, wherein said composition comprises a lyophilized powder or a liquid. 
     
     
         2 - 26 . (canceled) 
     
     
         27 . A method of preventing or treating a Respiratory Syncytial Virus (RSV) infection in a human, comprising administering to said human a composition that comprises a therapeutically effective amount of ALN-RSV01. 
     
     
         28 - 45 . (canceled) 
     
     
         46 . A method of preventing or treating a Respiratory Syncytial Virus (RSV) infection in a human lung transplant recipient, comprising administering to said human lung transplant recipient a composition comprising a therapeutically effective amount of ALN-RSV01. 
     
     
         47 . (canceled) 
     
     
         48 . The method of  claim 47 , wherein said administration is intranasal or intrapulmonary. 
     
     
         49 . (canceled) 
     
     
         50 . (canceled) 
     
     
         51 . The method of  claim 48 , wherein said intrapulmonary administration is by inhalation of said composition. 
     
     
         52 . The method of  claim 48 , wherein said composition is administered as an aerosol. 
     
     
         53 . The method of  claim 52 , wherein said aerosol is a nasal spray. 
     
     
         54 . The method of  claim 52 , wherein said aerosol is produced by a nebulizer. 
     
     
         55 . The method of  claim 54 , wherein said nebulizer is a PARI eFlow® 30 L nebulizer. 
     
     
         56 . The method of  claim 46 , comprising administering a plurality of doses of said composition. 
     
     
         57 . The method of  claim 56 , wherein one of said plurality of doses is administered daily. 
     
     
         58 . The method of  claim 57 , wherein said plurality of doses is two or three doses. 
     
     
         59 . The method of  claim 58 , wherein said plurality of doses is three doses. 
     
     
         60 . (canceled) 
     
     
         61 . The method of  claim 56 , wherein said human lung transplant recipient is presently infected with RSV when the first of said plurality of doses is administered. 
     
     
         62 . The method of  claim 46 , wherein said administering reduces RSV protein, RSV mRNA, RSV peak viral load, time to peak RSV viral load, duration of RSV viral shedding, RSV viral AUC, or RSV titer in a cell of the respiratory tract of said human lung transplant recipient. 
     
     
         63 . The method of  claim 56 , wherein said administering of said plurality of doses reduces RSV protein, RSV mRNA, RSV peak viral load, time to peak RSV viral load, duration of RSV viral shedding, RSV viral AUC, or RSV titer in a cell of the respiratory tract of said human lung transplant recipient to at least the same level as an administering of a single dose that equals the dose provided by said plurality of doses. 
     
     
         64 . The method of  claim 56 , wherein said administering of said plurality of doses is by inhalation and delivers a total dose of between 0.1 and 0.6 mg/kg of anhydrous oligonucleotide to said human lung transplant recipient. 
     
     
         65 . The method of  claim 46 , further comprising determining a characteristic of RSV infection, wherein said characteristic is selected from RSV mRNA, RSV peak viral load, time to peak RSV viral load, duration of RSV viral shedding, RSV viral AUC, or RSV titer. 
     
     
         66 . The method of  claim 65 , wherein said characteristic of RSV infection is determined by quantitative RT-PCR (qRT-PCR) analysis of a nasal swab sample and/or a sputum sample from said human lung transplant recipient. 
     
     
         67 . (canceled) 
     
     
         68 . The method of  claim 46 , wherein said human lung transplant recipient is receiving bronchodilator therapy. 
     
     
         69 . The method of  claim 68 , wherein said human lung transplant recipient is administered said composition within one hour of receiving bronchodilator therapy. 
     
     
         70 . (canceled) 
     
     
         71 . The method of  claim 46 , wherein ribavarin is administered to said human lung transplant recipient. 
     
     
         72 . The method of  claim 71 , wherein said human lung transplant recipient is administered said composition one to two hours before administration of ribavirin. 
     
     
         73 . The method of  claim 46 , wherein said administration of said composition to said human lung transplant recipient is started within seven days of onset of symptoms of RSV infection, wherein said symptoms comprise a decrease in FEV 1 , fever, new onset rhinorrhea, sore throat, nasal congestion, cough, wheezing, headache, myalgia, chills, or shortness of breath. 
     
     
         74 . The method of  claim 46 , wherein said administration of said composition improves FEV 1  or causes a reduction in one or more symptoms of RSV infection in said human lung transplant recipient relative to a placebo, wherein said symptoms are selected from the group consisting of fever, new onset rhinorrhea, sore throat, nasal congestion, cough, wheezing, headache, myalgia, chills, or shortness of breath. 
     
     
         75 . A method for reducing the risk of a medical condition in a human lung transplant recipient comprising preventing or treating a Respiratory Syncytial Virus (RSV) infection in a human lung transplant recipient by administering to said human lung transplant recipient a composition comprising a therapeutically effective amount of ALN-RSV01, wherein the medical condition is selected from the group consisting of acute rejection of transplanted lung, bronchilolitis obliterans syndrome, incidence of intubation, incidence of viral, bacterial, or fugal respiratory infection, and irreversible decline in lung function. 
     
     
         76 - 116 . (canceled)