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 modulating in vivo expression of a gene, comprising
 administering to a subject in need of delivery a composition comprising an mRNA encoding an enzyme, encapsulated within a liposome such that the administering of the composition results in the expression of the enzyme encoded by the mRNA in the liver,   wherein the liposome comprises one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol, and one or more PEG-modified lipids and has a size less than 150 nm.   
     
     
         128 . The method of  claim 127 , wherein the liposome comprises cationic lipids at a molar ratio of 20% to 70% of the total lipid. 
     
     
         129 . The method of  claim 128 , wherein the liposome comprises PEG-modified lipids at a molar ratio of 0.5% to 20% of the total lipid. 
     
     
         130 . The method of  claim 129 , wherein the liposome comprises non-cationic lipids at a molar ratio of 5% to 90% of the total lipid 
     
     
         131 . The method of  claim 130 , wherein the composition modulates gene expression in a target cell. 
     
     
         132 . The method of  claim 131 , wherein the target cell is a hepatocyte. 
     
     
         133 . The method of  claim 127 , wherein the composition is administered systemically. 
     
     
         134 . The method of  claim 127 , wherein the composition is administered intravenously. 
     
     
         135 . The method of  claim 127 , wherein administering the composition results in treatment of a disorder associated with an abnormal expression level of a protein. 
     
     
         136 . The method of  claim 130 , wherein one or more non-cationic lipids comprise DSPC. 
     
     
         137 . The method of  claim 130 , wherein one or more non-cationic lipids comprise DOPE. 
     
     
         138 . The method of  claim 130 , wherein one or more PEG-modified lipids comprise DMG-PEG-2000. 
     
     
         139 . The method of  claim 127 , wherein the mRNA is modified. 
     
     
         140 . The method of  claim 139 , wherein the mRNA comprises pseudouridines. 
     
     
         141 . The method of  claim 127 , wherein the mRNA comprises a 3′ untranslated region. 
     
     
         142 . The method of  claim 141 , wherein the mRNA comprises a cap structure. 
     
     
         143 . The method of  claim 142 , wherein the mRNA comprises a poly A tail. 
     
     
         144 . The method of  claim 127 , wherein the liposome has a size of less than 125 nm. 
     
     
         145 . The method of  claim 144 , wherein the liposome has a size of less than 100 nm. 
     
     
         146 . The method of  claim 127 , wherein the composition comprises one or more additional nucleic acids encapsulated within the liposome. 
     
     
         147 . The method of  claim 146 , wherein the one of more additional nucleic acids comprise RNA. 
     
     
         148 . The method of  claim 147 , wherein the RNA is a non-coding RNA.