Development of a Novel Method to Enhance Therapeutic Protein Production
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LIFESENSORS, INC., 271 GREAT VALLEY PKY, MALVERN, PA, 19355
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Phone: (610) 644-8845
AbstractDESCRIPTION (provided by applicant): The first step in any protein therapeutic exercise is expression of the protein. In some cases, this step is not troublesome. For increasing numbers of designer proteins and requirements for post-translation modificatio ns, however, enhanced expression and increasing protein yield have become very challenging tasks. Cost of goods is an important factor. In some cases therapeutic protein projects are abandoned because of an unreasonable cost of goods. It may come as a surp rise that companies spend 12-18 months to optimize the cell lines and improve the yield of recombinant proteins. Several approaches have been taken to overcome the expression problems; nevertheless, it is highly likely that no single technology or procedur e will be able to overcome the difficult-to-express protein problem. Selection of host, culture conditions and downstream processing can all play a role in the quality and quantity of product protein. LifeSensors has previously described a novel SUMO based fusion system. Attachment of SUMO to N-termini of inactive or poorly expressed proteins has led to a remarkable improvement in the functionality of proteins and 10-500-fold enhancement in protein production. Expression in prokaryotes yields an intact fusi on that is purified by virtue of a variety of affinity tags at the N-terminus of SUMO. SUMO-fusions are cleaved in vitro by a highly efficient SUMO protease to generate native protein with desired N-termini. However, a similar system is not available for h igher eukaryotic cells ,e.g., CHO that are primarily used for production of therapeutic antibodies and proteins. In this proposal we describe the development of related fusion system that will enhance the expression and secretion of difficult-to-express pr otein in CHO cells. With the advent of large numbers of engineered antibodies and therapeutic proteins as clinical candidates, protein expression has become a real bottleneck. Development of a system that improves quality and quantity of protein production by 10x fold will be a great advance in protein therapeutics. PUBLIC HEALTH RELEVANCE: Production of recombinant protein is a costly process. Increasing numbers of proteins are engineered to develop therapeutic products. It is becoming difficult to produce some of the proteins at a reasonable cost to the point that clinical projects are abandoned due to high cost of protein production. We have proposed the novel use of our previously demonstrated fusion proteins. Such a strategy would likely increase the quantity and quality of protein expression in therapeutics development.
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