CONTACT: JENNIFER BROWN
Iowa City IA 52242
(319) 335-9917; fax(319) 335-8034
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 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,"
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 http://www.targetedgenetics.com.
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.