title: Cell lines expressing mutant FX proteins to generate proteins with reduced rate of fucosylation: WO2010/141478.
abstract: BACKGROUND
  The application (WO 2010/141478) is in the field of glycobiology and deals with the synthesis of recombinant proteins with a reduced rate of fucosylation.
  
  
  OBJECTIVE
  It aims at generating mammalian cell lines that express mutant forms of GDP-4-keto-deoxy-mannose-3,5,-epimerase-4-reductase (FX) and cells that conditionally fucosylate proteins.
  
  
  METHODS
  Mutant forms of FX were synthesized, and mammalian cell lines genetically engineered to express mutant FX proteins and the protein of interest. Cell lines that conditionally fucosylate proteins were generated from a mutant FX form that has reduced ability to fucosylate glycoproteins at 37°C and not at 34°C.
  
  
  RESULTS
  Cells genetically engineered to express mutant forms of FX protein show reduced ability to fucosylate proteins, particularly antibodies, with rates as low as 5 - 0.5% fucosylation, compared to cells expressing wild-type FX.
  
  
  CONCLUSIONS
  Cells genetically engineered to express the mutant forms of FX protein provide a means to synthesize and express proteins with a reduced rate of fucosylation. The paradigm may be used to synthesize antibodies that mediate antibody-dependent cell-mediated cytotoxicity more efficiently. The application uses mammalian cell lines, genetically engineered to express mutant FX proteins, to synthesize and produce proteins with a reduced rate of fucosylation. The application claims the conditional control of protein fucosylation by FX mutant proteins.
authors.affiliation: Dublin City University, School of Biotechnology, Glasnevin, Dublin 9, Ireland. philippe.taupin@dcu.ie
authors.forename: Philippe
authors.initials: P
authors.lastname: Taupin
mesh_terms: D000818:Animals; D002238:Carbohydrate Epimerases / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005643:Fucose / Q000737:chemistry*; D005647:Fucosyltransferases / Q000378:metabolism; D005818:Genetic Engineering; D006023:Glycoproteins / Q000737:chemistry*; D006154:Guanosine Diphosphate Fucose / Q000378:metabolism; D006801:Humans; D007658:Ketone Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D050505:Mutant Proteins; D010330:Patents as Topic; D011994:Recombinant Proteins / Q000737:chemistry*; D013696:Temperature
chemical_list: D006023:Glycoproteins; D050505:Mutant Proteins; D011994:Recombinant Proteins; D006154:Guanosine Diphosphate Fucose; D005643:Fucose; D007658:Ketone Oxidoreductases; D005647:Fucosyltransferases; D002238:Carbohydrate Epimerases