Pegylated liposomes for delivery of immunogen encoding rna

Abstract

Nucleic acid immunisation is achieved by delivering RNA encapsulated within a PEGylated liposome. The RNA encodes an immunogen of interest. The PEG has an average molecular mass of between 1 kDa and 3 kDa. Thus the invention provides a liposome having a lipid bilayer encapsulating an aqueous core, wherein: (i) the lipid bilayer comprises at least one lipid which includes a polyethylene glycol moiety, such that polyethylene glycol is present on the liposome's exterior, wherein the average molecular mass of the polyethylene glycol is between 1 kDa and 3 kDa; and (ii) the aqueous core includes a RNA which encodes an immunogen. These liposomes are suitable for in vivo delivery of the RNA to a vertebrate cell and so they are useful as components in pharmaceutical compositions for immunising subjects against various diseases.

1 . A liposome within which RNA encoding an immunogen of interest is encapsulated, wherein the liposome comprises at least one lipid which includes a polyethylene glycol moiety, such that polyethylene glycol is present on the liposome's exterior, wherein the average molecular mass of the polyethylene glycol is between 1 kDa and 3 kDa. 
     
     
         2 . The liposome of  claim 1 , comprising PEG-DMG and/or a lipid of formula (X). 
     
     
         3 . The liposome of  claim 1 , wherein the liposome has a diameter in the range of 80-160 nm. 
     
     
         4 . The liposome of  claim 1 , wherein the liposome comprises a lipid with a cationic head group. 
     
     
         5 . The liposome of  claim 1 , wherein the liposome comprises a lipid with a zwitterionic head group. 
     
     
         6 . The liposome of  claim 1 , wherein the RNA is a self-replicating RNA. 
     
     
         7 . The liposome of  claim 6 , wherein the self-replicating RNA encodes (i) a RNA-dependent RNA polymerase which can transcribe RNA from the self-replicating RNA molecule and (ii) an immunogen. 
     
     
         8 . The liposome of  claim 7 , wherein the self-replicating RNA has two open reading frames, the first of which encodes an alphavirus replicase and the second of which encodes the immunogen. 
     
     
         9 . The liposome of  claim 6 , wherein the self-replicating RNA is 9000-12000 nucleotides long. 
     
     
         10 . The liposome of  claim 1 , wherein the immunogen can elicit an immune response in vivo against a bacterium, a virus, a fungus or a parasite. 
     
     
         11 . A pharmaceutical composition comprising a liposome of  claim 1 . 
     
     
         12 . A method for raising a protective immune response in a vertebrate, comprising the step of administering to the vertebrate an effective amount of the liposome of  claim 1 . 
     
     
         13 . The liposome of  claim 2 , wherein the liposome has a diameter in the range of 80-160 nm. 
     
     
         14 . The liposome of  claim 13 , wherein the liposome comprises a lipid with a cationic head group. 
     
     
         15 . The liposome of  claim 13 , wherein the liposome comprises a lipid with a zwitterionic head group. 
     
     
         16 . The liposome of  claim 13 , wherein the RNA is a self-replicating RNA.