Liver specific delivery of messenger rna

Abstract

Disclosed herein are compositions and methods of modulating the expression of gene or the production of a protein by transfecting target cells with nucleic acids. The compositions disclosed herein demonstrate a high transfection efficacy and are capable of ameliorating diseases associated with protein or enzyme deficiencies.

1 - 126 . (canceled) 
     
     
         127 . A composition comprising an mRNA encoding a protein or a peptide, encapsulated within a liposome,
 wherein the liposome has a size less than about 150 nm and comprises
 (i) one or more cationic lipids at a total molar ratio of 20% to 70% of the total lipids in the liposome, 
 (ii) one or more non-cationic lipids at a total molar ratio of 5% to 90% of the total lipids in the liposome, 
 (iii) one or more PEG-modified lipids at a total molar ratio of 0.5% to 20% of the total lipids in the liposome, and 
 (iv) cholesterol, and 
   wherein the mRNA comprises
 (i) a 5′-UTR, 
 (ii) a 3′-UTR, 
 (iii) a 5′ cap structure, and 
 (iv) a poly A tail. 
   
     
     
         128 . The composition of  claim 127 , wherein one or more non-cationic lipids comprise DSPC. 
     
     
         129 . The composition of  claim 127 , wherein one or more non-cationic lipids comprise DOPE. 
     
     
         130 . The composition of  claim 127 , wherein one or more PEG-modified lipids comprise DMG-PEG-2000. 
     
     
         131 . The composition of  claim 127 , wherein the 5′ cap structure comprises a Cap1 structure. 
     
     
         132 . The composition of  claim 127 , wherein the poly A tail comprises at least 90 nucleotides. 
     
     
         133 . The composition of  claim 127 , wherein the liposome has a size less than 125 nm. 
     
     
         134 . The composition of  claim 133 , wherein the liposome has a size less than 100 nm. 
     
     
         135 . The composition of  claim 127 , wherein the mRNA is modified. 
     
     
         136 . The composition of  claim 135 , wherein the mRNA comprises pseudouridines. 
     
     
         137 . The composition of  claim 127 , wherein administration of the composition into a subject results in the production of the peptide or protein in the subject.