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Release: Feb. 1, 2001

UI gene therapy technology licensed to Targeted Genetics Corporation

IOWA CITY, Iowa -- The University of Iowa Research Foundation has granted Targeted Genetics Corporation of Seattle a license to use certain gene therapy technologies developed at
the UI.

The agreement provides Targeted Genetics Corporation with access to technological developments from the laboratory of John Engelhardt, Ph.D., UI associate professor of anatomy and cell biology, and internal medicine, and director of the UI Center for Gene Therapy of Cystic Fibrosis and Other Genetic Diseases. These developments are positioned to expand the use of adeno-associated virus (AAV) as a vector for gene therapy. Targeted Genetics Corporation has also entered into a sponsored research agreement with the UI, which will result in funding for ongoing AAV research in Engelhardt's laboratory.

"I believe that AAV has enormous potential as a vector system for a wide variety of acquired and inherited diseases," Engelhardt said. "My laboratory has focused on characterizing basic mechanisms of recombinant AAV infection and applying this information to enhance and expand the utility of this already versatile vector."

He added, "I look forward to working with Targeted Genetics and believe that these new technologies will help to increase the number of diseases amenable to AAV-based gene therapy."

Gene therapy seeks to cure genetic diseases by replacing defective or disabled genes with a corrected gene. The correct genes are transported into cells by virus vectors such as AAV. Importantly, this virus has never been linked with any human disease. In addition, the genetically engineered version of AAV used by Engelhardt has had all of its viral genes removed. However, a major limitation of AAV is that it is too small to carry the large genes required to correct many genetic diseases. Engelhardt and his colleagues, UI research scientists Dongsheng Duan, Ph.D. and Ziying Yan, Ph.D., have developed several new strategies to overcome this limitation.

In practice, the genetic material is divided between two independent versions of AAV vectors. After the two viruses simultaneously enter a cell, their genetic material "joins hands" and rebuilds a "corrected" gene capable of producing high levels of the therapeutic protein.

"In essence, if one makes the analogy of a viral vector as a pickup truck carrying its genetic cargo into cells, we have created a system that divides the payload onto two trucks and provides the drivers with instructions on how to reassemble the payload once it gets to its destination. Accordingly, our dual vector system is capable of doubling the size of the genes it can deliver into cells," Engelhardt said.

For gene therapy to work effectively, the virus must deliver its genetic cargo to the nucleus of the cell, where the therapeutic protein is produced. However, the cell can circumvent this process, making gene delivery inefficient. In the case of AAV, the virus can be intercepted when it enters the cell and tagged with a molecule called ubiquitin.

"This molecular tagging marks AAV for 'curb side garbage pickup' and subsequent disposal into a cellular 'trash can' called the proteasome," Engelhardt said.

In a second strategy developed in Engelhardt's lab, and also licensed to Targeted Genetics Corporation, this disadvantageous tagging process can be disrupted, greatly increasing the efficiency by which AAV delivers its genes to the nucleus.

The UI Research Foundation, created in 1975, is a free-standing, not-for-profit corporation. Its mission is to enable the use of intellectual property created at the UI. The UI Research Foundation currently has more than 150 active licenses and, since its creation, has helped the UI to obtain more than 300 patents.

"We're delighted by the interest Targeted Genetics has shown in the work of Drs. Engelhardt, Duan, and Yan," said Bruce Wheaton, Ph.D., executive director of the UI Research Foundation. "We believe that our partnership with Targeted Genetics is a particularly good way of executing our mission since we are hopeful that the firm can help transform the discoveries of the Iowa researchers into beneficial medicines for a range of diseases."

Targeted Genetics Corporation develops gene therapy products for the treatment of acquired and inherited diseases. For more information about Targeted Genetics Corporation visit the company's Web site at

University of Iowa Health Care describes the partnership between the UI College of Medicine and the UI Hospitals and Clinics and the patient care, medical education and research programs and services they provide.