The challenge to produce more protein faster is leading to the development of new, engineered cell hosts and more tightly targeted ways of introducing genetic material to those hosts, as well as strategies that exert more precise control even at microtiter scale, according to speakers at the “Recombinant Protein Production” conference held in Vienna last month.
These advances are taking recombinant protein-expression systems beyond their traditional bacterial hosts to new, streamlined production systems that yield large quantities of high-quality protein faster and with fewer steps. The result is a more economical production system that also may help speed the overall project toward commercialization.
Oxyrane has developed a system to express biologics in the glyco-engineered yeast Yarrowia lipolytica. Wouter Vervecken, Ph.D., head of molecular biology, explained that the system was developed to express antibodies and lysosomal proteins with the correct glycosylation. “The latter are used for enzyme-replacement therapy,” he said. “The glycans on lysosomal proteins are important for targeting locations (lysosomes) within cells.”
“Typically, lysosomal proteins are produced in CHO cells,” which have many challenges and a low yield. “Perhaps 5% produce particles with the desired glycan structure,” Dr. Vervecken said. Using Oxyrane’s approach, more than 85% of the particles produced have the desired glycan structure. And, because they are produced in yeast, they avoid many of the issues associated with mammalian cell-based protein production.
“The benefits are improved yields and timelines, and decreased capital costs. These lysosomal proteins also outperform those that come out of other systems. We’re aiming for clinical benefit.” At dosages of 20 mg/kg of body weight, “we hope to decrease doses and complications.” He claimed that by precisely targeting a specific area of a cell, dosages can be reduced along with side effects, infusion time, and costs.
Preclinical work is promising, showing no significant problems, according to Dr. Vervecken. “We hope to have this in the clinic by early 2013.”