October 2006 - Pharmaceutical Technology

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October 2006

Pharmaceutical Technology


CELL CULTURE

Re-engineered Yeast Glycosylation System Might Replace Mammalian Cell Expression

Lebanon, NH (Sept. 7)—Scientists from GlycoFi, Inc. ( http://www.glycofi.com/), a wholly owned subsidiary of Merck & Co. (Whitehouse Station, NJ, http://www.merck.com/), in collaboration with Dartmouth-Hitchcock Medical Center, have engineered yeast cells capable of producing a broad range of recombinant therapeutic proteins with fully human sugar structures (glycosylation). Until now, these sugar structures, which ensure a glycoprotein's biological activity and half-life, required the expression of therapeutic glycoproteins from mammalian host cells.

As reported in the Sept. 8, 2006 issue of Science, the research team genetically engineered the Pichia pastoris yeast to secrete human glycoproteins with fully complex, terminally sialyated N-glycans. Recombinant erythropoietin, which stimulates the production of red blood cells, was successfully expressed using these yeast strains, purified, and its activity was demonstrated in vivo.

According to GlycoFi, the work "has the potential to eliminate the need for mammalian cell culture, while improving control over glycosylation and improving performance characteristics of many therapeutic proteins." The achievement follows a six-year study involving not only the elimination of yeast-specific glycosylation reactions, but also the introduction of 14 hetero-logous genes.

Yeast produces higher recombinant protein titers in shorter fermentation times compared with mammalian-culture systems. Yeast systems also do not have the risk of viral contamination associated with animal-based media. Tillman Gerngross, PhD, chief scientific officer of GlycoFi and professor of Bioengineering at Dartmouth College, says the advantages of yeast-expression technology "provide improvements in product uniformity and overall production economics. By engineering yeast to perform the final and most complex step of human glycosylation, we are now able to conduct far more extensive structure–function investigations on a much wider range of therapeutic protein targets."

–Maribel Rios

DRUG DELIVERY

Electric Pulse Delivers Nanoparticles, Biomolecules

Baltimore, MD (Sept. 10)—Researchers at Johns Hopkins University (JHU, http://www.jhu.edu/) have devised a new controlled-delivery system that applies an electrical pulse to release drug molecules, nanoparticles, biopolymers such as peptides and proteins, and protein assemblies such as viruses from thin fabricated gold electrodes. Led by Peter C. Searson, professor of material science and engineering at JHU, the scientists hope the technique someday will develop into a biocompatible implantable chip for precise and controlled dispensing of small amounts of drug into the body.

The researchers constructed long chains of hydrocarbon molecules. One end of the chain was anchored by a gold–sulfur bond to specially designed gold electrodes, each the width of a single human hair. The biomolecule to be released was attached to the other end. When a brief electrical pulse was sent through wires attached to each electrode, it broke the bond between the sulfur atoms and the gold platform, causing the tethered molecule to be released at a precise time.

The technology reportedly has several advantages over similar delivery techniques. "Because our molecules are attached to a surface, we can work with much smaller concentrations. We've also shown that our system is reusable. After a group of molecules is released, you can easily attach new molecules to an electrode and use it again," says Searson.

–Maribel Rios

IN MEMORIAM

Arthur R. Mlodozeniec, Consultant and Lecturer, Dies

Menlo Park, CA (Sept. 4)—Arthur R. Mlodozeniec, PhD, a noted lecturer and consultant and member of Pharmaceutical Technology's Editorial Advisory Board, died on Sept. 4 at his home in Menlo Park, California. He was 69 years old.

His death was announced by his son-in-law, James McCormick.


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