Synthetic Nanostructures Including Nucleic Acids and/or Other Entities

Abstract

Articles, compositions, kits, and methods relating to nanostructures, including synthetic nanostructures, are provided. Certain embodiments described herein include structures having a core-shell type arrangement; for instance, a nanostructure core may be surrounded by a shell including a material, such as a lipid bilayer, and may include other components such as oligonucleotides. In some embodiments, the structures, when introduced into a subject, can be used to deliver nucleic acids and/or can regulate gene expression. Accordingly, the structures described herein may be used to diagnose, prevent, treat or manage certain diseases or bodily conditions. In some cases, the structures are both a therapeutic agent and a diagnostic agent.

What is claimed is: 
     
         1 - 99 . (canceled) 
     
     
         100 . A synthetic nanostructure for in vivo delivery of a nucleic acid to a cell, the synthetic nanostructure comprising:
 a core;   a shell comprising a lipid, the shell surrounding the core;   a nucleic acid that is non-covalently associated with the core, the shell, or both the core and the shell; and   wherein the synthetic nanostructure, when introduced into a subject, delivers the nucleic acid to cytoplasm of cells of the subject.   
     
     
         101 . The synthetic nanostructure according to  claim 100 , wherein the nucleic acid comprises ribonucleic acid (RNA). 
     
     
         102 . The synthetic nanostructure according to  claim 101 , wherein the nucleic acid comprises mRNA. 
     
     
         103 . The synthetic nanostructure according to  claim 100 , wherein the nucleic acid comprises an end modification or a modification to the backbone or base portion to increase stability or facilitate association with the core. 
     
     
         104 . The synthetic nanostructure according to  claim 100 , wherein the nucleic acid is sequestered within the shell to reduce exposure to the surface of the nanostructure. 
     
     
         105 . The synthetic nanostructure according to  claim 104 , wherein the nucleic acid is associated with a surface of the core or an interior of the core. 
     
     
         106 . The synthetic nanostructure according to  claim 105 , wherein the nucleic acid is physisorbed to the core. 
     
     
         107 . The synthetic nanostructure of  claim 100 , wherein the structure has a largest cross-sectional dimension of less than or equal to about 100 nm. 
     
     
         108 . The synthetic nanostructure according to  claim 100 , wherein the shell further includes cholesterol. 
     
     
         109 . The synthetic nanostructure according to  claim 100 , wherein the shell comprises a phospholipid. 
     
     
         110 . The synthetic nanostructure according to  claim 109 , wherein the phospholipid comprises di-stearoyl-phosphatidylcholine (DSPC). 
     
     
         111 . The synthetic nanostructure of  claim 100 , wherein the core comprises an organic material. 
     
     
         112 . The synthetic nanostructure of  claim 111 , wherein the organic material is a lipid, a synthetic polymer, or a natural polymer. 
     
     
         113 . The synthetic nanostructure of  claim 100 , wherein the core is hollow or partially hollow. 
     
     
         114 . The synthetic nanostructure of  claim 100 , further comprising polyethylene glycol (PEG). 
     
     
         115 . A composition comprising the synthetic nanoparticle according to  claim 100  and a buffer. 
     
     
         116 . A pharmaceutical composition comprising the synthetic nanostructure of  claim 100  and a pharmaceutically acceptable carrier. 
     
     
         117 . The synthetic nanostructure according to  claim 100 , further comprising an apolipoprotein associated with the lipid shell or core. 
     
     
         118 . The synthetic nanostructure of  claim 117 , wherein the apolipoprotein is selected from the group consisting of apolipoprotein A, apolipoprotein B (e.g., apo B48 and apo B100), apolipoprotein C and apolipoproteins D, apolipoprotein E, and apolipoprotein H. 
     
     
         119 . A method of delivering an mRNA to a cell comprising contacting the cell with the synthetic nanostructure of  claim 100 . 
     
     
         120 . A method of delivering an mRNA to cells of a subject, comprising administering to the subject the synthetic nanostructure of  claim 100 . 
     
     
         121 . The method of  claim 120 , wherein apolipoprotein associates with the nanostructure after administration to the subject. 
     
     
         122 . The method of  claim 120 , wherein the synthetic nanostructure is administered intramuscularly.