G-CSF Transferrin Fusion Proteins

Abstract

A polypeptide comprising a G-CSF domain operably linked to a Tf domain, wherein the ability of the polypeptide to be transported into a cell expressing a TfR gene or the ability of the polypeptide to be transported across a cell expressing a TfR gene via transcytosis is higher than that of the G-CSF domain alone.

1 - 11 . (canceled) 
     
     
         12 . A nucleic acid comprising a DNA sequence encoding a recombinant polypeptide comprising a granulocyte colony stimulating factor (G-CSF) domain operably linked to a transferring (Tf) domain, wherein the ability of the polypeptide to be transported into a cell expressing a transferring receptor (TfR) gene or the ability of the polypeptide to be transported across a cell expressing a TfR gene via transcytosis is higher than that of the G-CSF domain alone. 
     
     
         13 . A cell comprising the nucleic acid of  claim 12 . 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . A composition comprising a pharmaceutically acceptable carrier and the nucleic acid of  claim 12 . 
     
     
         17 . A method of producing a polypeptide, comprising cultivating the cell of  claim 13  under conditions that allow expression of the polypeptide. 
     
     
         18 . The method of  claim 17 , further comprising collecting the polynucleotide. 
     
     
         19 - 30 . (canceled) 
     
     
         31 . The polypeptide of  claim 12 , wherein the G-CSF domain and the Tf domain are linked through covalent bonding. 
     
     
         32 . The polypeptide of  claim 31 , wherein the G-CSF domain and the Tf domain are linked through a disulfide bond. 
     
     
         33 . The polypeptide of  claim 12 , wherein the G-CSF domain is linked to the Tf domain through a linker. 
     
     
         34 . The polypeptide of  claim 12 , wherein the G-CSF domain is linked to the Tf domain through a Leu-Glu linker. 
     
     
         35 . The polypeptide of  claim 12 , further comprising a secretion signal at the N-terminus. 
     
     
         36 . The polypeptide of  claim 12 , wherein the order of the G-CSF domain and the Tf domain is from the N-terminus to the C-terminus. 
     
     
         37 . The method of producing a polypeptide according to  claim 17 , comprising contacting the polypeptide with iron such that the recombinant polypeptide is loaded with iron. 
     
     
         38 . The cell according to  claim 13 , further comprising iron.