Capped and uncapped rna molecules and block copolymers for intracellular delivery of rna

Abstract

The present invention relates to the use of at least one tetrafunctional non-ionic amphiphilic block copolymer as a vehicle for capped or uncapped mRNA for intracellular delivery for gene therapy.

1 - 17 . (canceled) 
     
     
         18 . A method for intracellular delivery, comprising one or more than one administration to a subject of a composition comprising a tetrafunctional non-ionic amphiphilic block copolymer as a vehicle for capped or uncapped mRNA; wherein said tetrafunctional non-ionic amphiphilic block copolymer comprises hydrophilic blocks comprising polyethylene oxide units and hydrophobic blocks comprising polypropylene oxide units, and is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         and mixtures thereof. 
       
     
     
         19 . The method according to  claim 18 , wherein said mRNA is a modified mRNA. 
     
     
         20 . The method according to  claim 18 , wherein said mRNA is a capped and modified mRNA. 
     
     
         21 . The method according to  claim 18 , wherein said mRNA is a messenger  5′ppp RNA,  5′pp RNA,  5′p RNA or  5′OH RNA. 
     
     
         22 . The method according to  claim 18 , wherein said tetrafunctional non-ionic amphiphilic block copolymer is selected from: 
       
         
           
           
               
               
           
         
         and mixtures thereof. 
       
     
     
         23 . The method according to  claim 18 , wherein said tetrafunctional non-ionic amphiphilic block copolymer is: 
       
         
           
           
               
               
           
         
       
     
     
         24 . The method according to  claim 18 , wherein said tetrafunctional non-ionic amphiphilic block copolymer is: 
       
         
           
           
               
               
           
         
       
     
     
         25 . The method according to  claim 18 , wherein said tetrafunctional non-ionic amphiphilic block copolymer is: 
       
         
           
           
               
               
           
         
       
     
     
         26 . The method according to  claim 18 , wherein at least one terminal block of the tetrafunctional non-ionic amphiphilic block copolymer is glycosylated and/or functionalized. 
     
     
         27 . The method according to  claim 18 , wherein said tetrafunctional non-ionic amphiphilic block copolymer comprises at least one terminal hydrophilic or hydrophobic block conjugated with at least one glycosyl moiety. 
     
     
         28 . The method according to  claim 18 , wherein said method comprises more than one administration to the subject of the composition comprising a tetrafunctional non-ionic amphiphilic block copolymer. 
     
     
         29 . The method according to  claim 19 , wherein said method comprises more than one administration to the subject of the composition comprising a tetrafunctional non-ionic amphiphilic block copolymer. 
     
     
         30 . A pharmaceutical composition comprising a tetrafunctional non-ionic amphiphilic block copolymer, in combination with at least one capped modified mRNA or uncapped modified mRNA; wherein said tetrafunctional non-ionic amphiphilic block copolymer comprises hydrophilic blocks comprising polyethylene oxide units and hydrophobic blocks comprising polypropylene oxide units, and is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         and mixtures thereof. 
       
     
     
         31 . The pharmaceutical composition according to  claim 30 , wherein the tetrafunctional non-ionic amphiphilic block copolymer comprises at least one terminal block which is glycosylated and/or functionalized. 
     
     
         32 . The pharmaceutical composition according to  claim 30 , wherein said tetrafunctional non-ionic amphiphilic block copolymer and mRNA are formulated in a Tyrode's medium or an equivalent medium. 
     
     
         33 . A method for increasing, improving, and/or maintaining the expression of a protein in an eukaryotic host, comprising a step of transfecting into said host at least one tetrafunctional non-ionic amphiphilic block copolymer, as a vehicle for at least one capped or uncapped mRNA; wherein said tetrafunctional non-ionic amphiphilic block copolymer comprises hydrophilic blocks comprising polyethylene oxide units and hydrophobic blocks comprising polypropylene oxide units, and is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         and mixtures thereof. 
       
     
     
         34 . A tetrafunctional non-ionic amphiphilic block copolymer of formula: 
       
         
           
           
               
               
           
         
         or one of its pharmaceutically acceptable salts. 
       
     
     
         35 . The tetrafunctional non-ionic amphiphilic block copolymer according to  claim 34 , comprising at least one terminal block which is glycosylated and/or functionalized. 
     
     
         36 . The tetrafunctional non-ionic amphiphilic block copolymer according to  claim 35 , comprising at least one terminal block which is glycosylated and/or functionalized.