Open Competition 1 - Biotechnology
Production of Therapeutic Proteins Through Metabolic Engineering of Yeast
Genetically engineer yeast to add sugars to proteins in a "human-like" rather than "yeast-like" pattern, creating a platform technology for large-scale, low-cost production of therapeutic proteins.
Sponsor: GlycoFi, Inc.21 Lafayette Street
Lebanon, NH 03766
GlycoFi proposes to develop a new biotech "platform" based on genetically engineered yeast to more efficiently produce a large portfolio of therapeutic proteins that are more efficacious and have less potential for immunogenic problems. Advances in genomics and proteomics have fueled an explosive growth in pharmaceutical research into tailored, therapeutic proteins to combat disease. This potential bonanza of powerful new drug therapies faces a possibly serious bottleneck in production capacity, however. Proteins are complex biological molecules that cannot be made by simple chemical synthesis like traditional drugs -- they are manufactured by living cells or organisms that have been genetically engineered to produce a particular protein product. The problem is complicated further by the fact that higher mammals naturally attach certain specific sugars to their proteins in a specific way -- a process known as glycosylation. The sugars on genetically engineered proteins made by certain micro-organisms may be different and are attached in a different way, so these proteins are recognized by human systems as "foreign." Unless the organisms also provide human-like glycosylation, the usefulness of the proteins may be severely limited. Currently, therapeutic proteins and peptides are produced mostly from mammalian cell lines, from Chinese hamster ovaries, and mouse myeloma cells, which can produce proteins with human-like glycosylation. These sources are costly and have limited productivity. In principle, genetically engineered yeasts could quickly produce large quantities of many human proteins at relatively low cost and without the complications introduced by using mammalian cells -- except for the glycosylation problem. GlycoFi plans to produce an engineered strain of yeast that can be modified at will to produce a large range of human proteins, and that provides human-like glycosylation. Tailoring a yeast strain to produce a specific protein is a widely recognized technique in biotechnology, but changing the yeast's natural glycosylation system represents a major new challenge. Because glycosylation is a complex process over and above the initial production of a given protein, the task will require major changes to the yeast's metabolic system, and the targeted replacement of many genes that play a role in the process. While the company has preliminary results that suggest the goal is feasible, it is not entirely certain that yeast can survive and reproduce with its entire natural glycosylation system changed. GlycoFi is a start-up company with limited resources, and ATP support will accelerate the work by up to two years. If successful, the yeast-based platform should outperform current cell culture technology by a factor of 20, producing valuable therapeutic proteins at a tenth the cost and in a quarter of the time -- potentially saving up to $675 million in drug development over the next seven years and enabling significant capacity increases in the production of vaccines and monoclonal antibodies.