Method of enhancing expression of recombinant proteins

Introduction Large scale production of industrially and medically important proteins is achieved using
“expression systems”, whereby a gene encoding the protein of choice is introduced into a cell (e.g. yeast or bacterial) that is optimized for high-yield expression. Many proteins are poorly produced in bacterial cells for reasons that are usually attributed to "codon usage". Most mammalian proteins are encoded by genes that use "AT-rich" codons whereas most proteins in E. coli use codons that are "GC-rich". One solution is to convert all of the AT-rich codons in the gene to their GC-rich counterparts; a costly and time-consuming procedure. Technology description University of Washington scientists have determined that bacteria possess a system to repress expression from AT-rich DNA, a phenomenon termed “xenogenetic silencing” (or XS). This invention provides a bacterial strain that lacks the XS system and therefore is unable to silence AT-rich foreign DNA. Expression of AT-rich genes in the mutant strain is as much as fifteen-fold higher than expression in wild-type strains. Business Opportunity More than 325 million people worldwide have been helped by the more than 155 recombinantly produced polypeptides and peptides (drugs and vaccines) currently approved by the FDA. In addition, there are more than 370 biotechnology drug products and vaccines currently in clinical trials targeting more than 200 diseases, including: various cancers, Alzheimer’s disease, heart disease, diabetes, multiple sclerosis, AIDS and arthritis. However, development and manufacturing of therapeutically useful polypeptides has been hampered, in large part, by the limitations of the organisms currently used to express these exogenous polypeptides. This new invention will dramatically facilitate the production of crucial proteins and thereby provide additional therapeutic opportunities. Intellectual Property Position The University has applied for patent protection to secure the rights to this technology. Related Publication(s)
Science 2006 Jul 313:236-238

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