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 method of delivery of messenger RNA (mRNA) for in vivo production of a protein or a peptide, comprising administering to a subject in need of delivery a composition comprising an mRNA encoding the protein or the peptide, encapsulated within a liposome such that the administering of the composition results in the systemic expression of the protein or the peptide encoded by the mRNA, wherein the mRNA comprises:
 (i) a 5′-UTR,   (ii) a 3′-UTR,   (iii) a 5′ cap structure, and   (iv) a poly A tail, and   wherein the liposome comprises:   (i) one or more cationic lipids at a molar ratio of 20% to 70% of the total lipids present in the liposome,   (ii) a non-cationic lipid of DSPC or DOPE at a molar ratio of 5% to 90% of the total lipids in the liposome,   (iii) a PEG-modified lipid of DMG-PEG 2000 at a molar ratio of 0.5% to 20% of the total lipids in the liposome, and   (iv) cholesterol, and   wherein the liposome has a size less than 150 nm.   
     
     
         128 . The method of  claim 127 , wherein one or more non-cationic lipids comprise DSPC. 
     
     
         129 . The method of  claim 127 , wherein one or more non-cationic lipids comprise DOPE. 
     
     
         130 . The method of  claim 127 , wherein the composition is administered systemically. 
     
     
         131 . The method of  claim 127 , wherein the composition is administered intramuscularly. 
     
     
         132 . The method of  claim 127 , wherein the composition is administered subcutaneously. 
     
     
         133 . The method of  claim 127 , wherein the systemic expression results in the expression of the encoded protein or peptide at a target tissue distant from an injection site. 
     
     
         134 . The method of  claim 127 , wherein the mRNA is modified. 
     
     
         135 . The method of  claim 134 , wherein the mRNA comprises pseudouridines. 
     
     
         136 . The method of  claim 127 , wherein the mRNA comprises a 3′ untranslated region. 
     
     
         137 . The method of  claim 136 , wherein the mRNA comprises a cap structure. 
     
     
         138 . The method of  claim 137 , wherein the cap structure is a Cap1. 
     
     
         139 . The method of  claim 136 , wherein the mRNA comprises a poly A tail. 
     
     
         140 . The method of  claim 127 , wherein the liposome has a size of less than 125 nm. 
     
     
         141 . The method of  claim 127 , wherein the liposome has a size of less than 100 nm. 
     
     
         142 . The method of  claim 127 , wherein the administering of the composition confers immunity to a subject. 
     
     
         143 . The method of  claim 133 , wherein the target tissue comprises muscle cells. 
     
     
         144 . The method of  claim 143 , wherein the muscles cells are skeletal muscle cells, or vascular smooth muscle cells.