High Molecular Weight Heparosan Polymers and Methods of Production and Use Thereof

Abstract

High molecular weight heparosan polymers are described, as are methods of producing and using the high molecular weight heparosan polymers.

What is claimed is: 
     
         1 . A biomaterial composition, the composition comprising:
 an isolated heparosan polymer, wherein the isolated heparosan polymer is biocompatible with a mammalian patient and biologically inert in extracellular compartments of a mammalian patient, the isolated heparosan polymer being represented by the structure (-GlcUA-beta1,4-GlcNAc-alpha-1,4-) n , wherein n is a positive integer greater than or equal to 2,000.   
     
     
         2 . The biomaterial composition of  claim 1 , wherein n is in a range of from about 2,000 to about 17,000. 
     
     
         3 . The biomaterial composition of  claim 1 , wherein the heparosan polymer is linear. 
     
     
         4 . The biomaterial composition of  claim 1 , wherein the heparosan polymer is crosslinked. 
     
     
         5 . The biomaterial composition of  claim 1 , further defined as being in a gel, semi-solid, and/or particulate state, and wherein the biomaterial composition is further defined as being an implantable biomaterial composition. 
     
     
         6 . The biomaterial composition of  claim 1 , further defined as being a liquid biomaterial composition, and wherein the biomaterial composition is further defined as being an injectable biomaterial composition. 
     
     
         7 . The biomaterial composition of  claim 1 , further comprising a substrate to which the isolated heparosan polymer is covalently and/or non-covalently attached. 
     
     
         8 . The biomaterial composition of  claim 7 , wherein the substrate is selected from the group consisting of silica, silicon, semiconductors, glass, polymers, nanotubes, nanoparticles, organic compounds, inorganic compounds, metals, and combinations thereof. 
     
     
         9 . The biomaterial composition of  claim 8 , wherein at least a portion of the substrate is a metal selected from the group consisting of gold, copper, stainless steel, nickel, aluminum, titanium, thermosensitive alloys, and combinations thereof. 
     
     
         10 . The biomaterial composition of  claim 1 , wherein the isolated heparosan polymer is substantially not susceptible to mammalian hyaluronidases or heparanases and thereby is not substantially degraded in vivo in extracellular compartments of a mammalian patient. 
     
     
         11 . An isolated nucleotide sequence encoding a polypeptide having heparosan synthase activity, wherein at least one of:
 (a) the polypeptide having heparosan synthase activity is at least 90% identical to at least one of SEQ ID NOS:2, 4, and 6-8, and the nucleotide sequence encoding the polypeptide has been gene-optimized for expression in the recombinant host cell; and   (b) the polypeptide having heparosan synthase activity has 1-20 amino acid additions, deletions, and/or substitutions when compared to at least one of SEQ ID NOS:2, 4, and 6-8, and the nucleotide sequence encoding the polypeptide has been gene-optimized for expression in the recombinant host cell;   (c) the polypeptide is encoded by the nucleotide sequence of at least one of SEQ ID NOS:9-11; and   (d) the polypeptide is encoded by a nucleotide sequence that is at least 90% identical to at least one of SEQ ID NOS:9-11.   
     
     
         12 . The isolated nucleotide sequence of  claim 11 , wherein the host cell for which the nucleotide sequence has been gene-optimized is  E. coli.    
     
     
         13 . A recombinant host cell, comprising the isolated nucleotide sequence of  claim 11 . 
     
     
         14 . The recombinant host cell of  claim 13 , further defined as an  E. coli  recombinant host cell.