Protein-polymer nanoassemblies and intracellular protein delivery

Abstract

The invention provides novel polymer-protein conjugates and molecular assemblies for controlled intracellular delivery of proteins, and compositions and methods of preparation and use thereof.

1 - 20 . (canceled) 
     
     
         21 . A polymer-protein conjugate, comprising: a copolymer comprising a first monomer of PEG-methacrylate (PEG-MA) and a second monomer of methacrylate having a side chain conjugated to a protein via a degradable linker. 
     
     
         22 . The polymer-protein conjugate of  claim 21 , wherein the degradable linker is sensitive to reactive oxygen species, a reducing environment, or change in pH. 
     
     
         23 . The polymer-protein conjugate of  claim 22 , wherein the degradable linker comprises a boronate ester linker. 
     
     
         24 . The polymer-protein conjugate of  claim 22 , wherein the degradable linker comprises a disulfide linker. 
     
     
         25 . The polymer-protein conjugate of  claim 22 , wherein the degradable linker comprises a cis-aconityl linker. 
     
     
         26 . A molecular assembly comprising the polymer-protein conjugate of  claim 21 . 
     
     
         27 . The molecular assembly of  claim 26 , wherein the polymer:protein ratio by weight is in the range from about 1:1 to about 50:1. 
     
     
         28 . The molecular assembly of  claim 26 , wherein the polymer-protein conjugate is adapted to release the protein for its native function upon degradation of the degradable linker. 
     
     
         29 . The molecular assembly of  claim 28 , wherein the polymer-protein conjugate is adapted to release the protein in the presence of a specific and biologically relevant stimulus inside cells. 
     
     
         30 . The molecular assembly of  claim 29 , wherein the polymer-protein conjugate is adapted to release the protein in the presence of a specific and biologically relevant stimulus in the cytosol. 
     
     
         31 . The molecular assembly of  claim 27 , wherein the protein has a molecular weight in the range of about 10 kDa to about 500 kDa. 
     
     
         32 . The molecular assembly of  claim 31 , wherein the protein has an isoelectric points (pI) in the range of about 3.0 to about 12.0. 
     
     
         33 . A composition comprising the molecular assembly of  claim 26 . 
     
     
         34 - 54 . (canceled)