February 19, 2009
New biologics center to advance personalized drug delivery
By Nedra Pautler
Department of Bioengineering
A new interdisciplinary center based in the UW Department of Bioengineering will work on guiding biologically based drugs to targets inside the cell. Patrick Stayton, UW professor of bioengineering, has been awarded $7.2 million over four years from Washington’s Life Science Discovery Fund to establish a center that will address one of the biggest challenges facing drug development today: delivering biological molecules — proteins, DNA, RNA — inside diseased cells so they can attack intracellular targets. Being able to do this successfully could enable new classes of drugs for treatment of cancer and inflammatory diseases.
The new Center for Intracellular Delivery of Biologics in the Department of Bioengineering will bring together a team of pharmaceutical scientists, medicinal chemists, chemical engineers, and clinical researchers from the School of Medicine, College of Engineering, School of Pharmacy, and the Fred Hutchinson Cancer Research Center.
“We are still at a very early stage, but if we solve this difficult challenge with safe and effective biologic carriers, we would open up a new universe of intracellular treatment targets that are currently inaccessible,” Stayton said.
The long-term goals are new classes of biological drugs to more effectively treat patients, fresh drug delivery technologies and therapeutics to spawn new start-up companies in Washington, and student training in one of the hottest areas in biotechnology.
“Ultimately, we would like to see Seattle regarded as the clear leader of biologic therapeutics development — in research and education — and help build an even stronger biotechnology industry in the region,” Stayton said.
The challenge is to engineer what nature has already learned to do. Pathogens, Stayton explained, have evolved clever delivery systems for navigating through the body and then through cell membranes so they can find their intracellular targets. But the biotechnology and pharmaceutical industries currently do not have similarly efficient delivery vehicles for getting biological molecules to the right place inside of target cells. It will take a village of scientists — chemists, engineers, pharmacists and others — to transform biological drugs into the life-affirming intracellular sharpshooters they could be, he said.
Stayton assembled the complex scientific team necessary to take on the challenge and, eventually, develop new early stage therapeutic candidates. By building on UW Bioengineering’s strong interdisciplinary nature, the new center will boost cross-discipline collaboration and translational, or clinically useful, research.
Biologics — drugs based on those used by living organisms — are large by molecular standards, weighing thousands of times more than the small molecules scientists can now move inside cells. Their size plus their strong electrical charge make them very difficult to move through the outer membrane that all cells use to control access to the intracellular compartments. Current biologic drugs can hit the mark on the exterior cell wall, but successfully targeting them to targets inside the cell is “the grand challenge,” Stayton says. Biologic drugs include antibodies, gene silencing DNA and RNA, and vaccines.
In current delivery methods, drugs can get lost, Stayton said, and not reach the specific area within a patient’s body or access the right place inside of diseased cells to have the best effect. On the other hand, viruses and pathogens, like diphtheria, are terrific navigators, traveling right to their target and delivering their protein, DNA, or RNA highly effectively inside of cells.
“These pathogens have remarkable molecular machines that enhance transport of DNA, RNA, or proteins across the cell membrane to the proper locations inside their target cells,” Stayton said.
By mimicking aspects of pathogen behavior, Stayton’s group, working with Bioengineering Professor Allan Hoffman, has created synthetic polymers that may pass through cell walls and land on the designated spot to offer more effective treatment. These smart polymers, as they are called, sense their environment and change properties to deliver biologic drugs inside cells.
The center will incorporate three core areas: smart delivery systems (designing and synthesizing new carriers for biologic drugs); analytical biopharmacy (using cutting-edge instruments to optimize pharmaceutical properties of new drugs); and pre-clinical models (characterizing drug activity in disease models). In addition, a new “catalyst” program will bring the center together with local biotechnology companies and the Institute of Translational Health Sciences through an advisory board to help point the research toward the highest impact needs.
He envisions the center as a translational catalyst between the world-class biomedical research at UW and FHCRC, and the development-oriented research of engineering and pharmacy.
Through the center, students from bioengineering and other departments will work on real-life challenges faced in developing biologic drugs from discovery to application. Stayton predicts that with this training they will find better job opportunities in the biotechnology world.
The initial faculty team includes nine collaborators: four from bioengineering, two from medicinal chemistry, one from chemical engineering, one from the UW’s Center for Lung Biology, and one from the Fred Hutchinson Cancer Research Center.
This is Stayton’s second Life Science Discovery Fund award and the third for a UW bioengineering faculty member. In 2008, Stayton was awarded nearly $1 million for self-powered smart cards for diagnostic screening. At the same time, Cecilia Giachelli was awarded $1.5 million to develop cell therapy technologies to inhibit tissue calcification. Tissue calcification diminishes joint, valve, blood vessel, and muscle function. Currently there is no treatment for the condition.
The Life Sciences Discovery Fund was established by Gov. Chris Gregoire in 2005 to support innovative research to “promote life sciences competitiveness, enhance economic vitality, and improve health and health care” in Washington. Funding for the agency’s grant competitions comes from Washington’s allocation of bonus payments under the Master Tobacco Settlement of 1998, revenues arising from multi-state litigation with U.S. tobacco companies.
