Dlin-mc3-dma lipid nanoparticle delivery of modified polynucleotides

Abstract

The present disclosure provides, inter alia, formulation compositions comprising modified nucleic acid molecules which may encode a protein, a protein precursor, or a partially or fully processed form of the protein or a protein precursor. The formulation composition may further include a modified nucleic acid molecule and a delivery agent. The present invention further provides nucleic acids useful for encoding polypeptides capable of modulating a cell's function and/or activity.

What is claimed is: 
     
         1 . A method for producing a protein of interest in a mammal comprising contacting said mammal with a modified mRNA formulated in a lipid nanoparticle comprising a cationic lipid, wherein the cationic lipid is DLin-MC3-DMA. 
     
     
         2 . The method of  claim 1  wherein the lipid nanoparticle has a final total molar ratio of 50 mol % DLin-MC3-DMA, 10 mol % DSPC, 38.5 mol % Cholesterol and 1.5 mol % of PEG lipid. 
     
     
         3 . The method of  claim 2 , wherein the lipid nanoparticle has a 20:1 weight ratio of total lipid to the modified RNA. 
     
     
         4 . The method of  claim 3 , wherein the PEG lipid is PEG-c-DOMG. 
     
     
         5 . The method of  claim 4 , and wherein said protein of interest is expressed for at least 24 hours. 
     
     
         6 . The method of  claim 4 , wherein the mammal is contacted with modified RNA at a dose selected from the group consisting of 0.005 mg/kg, 0.05 mg/kg and 0.5 mg/kg. 
     
     
         7 . The method of  claim 1 , wherein the modified mRNA comprises at least one nucleoside modification.