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Pitt Researchers Construct Novel Delivery System For Gene Therapy Of Liver Disorders

PITTSBURGH, Dec. 18 -- Like a car that transports its passengers, layers of lipids form a protective barrier for their passenger DNA molecules, safely whisking them past DNA-degrading enzymes and quickly delivering them to their destinations, or target cells.

A research team from the University of Pittsburgh has constructed the first prototype of this "car," a delivery mechanism for genes called a reconstituted chylomicron remnant (RCR) that has resulted in the extended production of therapeutic proteins in an animal model, according to a report published in the Dec. 23 Proceedings of the National Academy of Sciences.

The research was developed in collaboration with Targeted Genetics Corporation, Seattle, and the RCR Vector is exclusively licensed to Targeted Genetics.

In the study, Pitt researchers detailed how they coated twisted strands of DNA encoding for the a1-antitrypsin (hAAT) gene with lipids and added oil to form stable RCR structures with 65 percent of DNA incorporated into the oil core.

"We have developed the first non-viral vector that resembles a naturally occurring lipoprotein," stated Leaf Huang, Ph.D., professor of pharmacology at the University of Pittsburgh. Typically, lipoproteins pick up fat and take it to the liver where it is released and processed.

"In our studies, we placed genes into the RCR structures instead of fat and found that these genes were released into liver cells and their blueprints were used to build new proteins," added Dr. Huang. "Mimicking the body's own transport system, we have created a model in which we have used a good copy of hAAT to show that RCRs are a great way to get genes into cells and direct the body's cellular machinery to produce therapeutic proteins." A bad copy of the hAAT gene is thought to cause pulmonary emphysema and liver disease. Introducing a good copy into target cells
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Contact: Amy Kemp
kempam@a1.isd.upmc.edu
(412) 624-2607
University of Pittsburgh Medical Center
22-Dec-1997


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