CONTACT: BECKY SOGLIN
2130 Medical Laboratories
Iowa City IA 52242
(319) 335-6660; fax (319) 335-8034
Release: March 20, 2000
UI researchers find potential way to improve gene therapy delivery to
IOWA CITY, Iowa -- Developing successful gene therapy for neurodegenerative
diseases that affect a large proportion of the brain is challenging. One hurdle
involves ensuring that the gene vectors -- disabled viruses that carry the
genes -- are well distributed in the brain and efficiently deposit the genes
in the target cells. However, University of Iowa and National Institutes of
Health (NIH) investigators have collaborated to find that a certain gene vector
can effectively reach many brain sites following a single injection.
The finding, based on animal models, recently appeared online at the website
of the Proceedings of the National Academy of Sciences (PNAS). The print article
will appear in the March 28 issue of the Proceedings.
"We did not believe that multiple injections of the gene therapy vector
was the answer to achieving widespread distribution throughout the brain,"
said Beverly Davidson, Ph.D., UI professor of internal medicine and the study's
lead investigator. "From previous work using tissue culture, we believed
that different types of adeno-associated virus (AAV) vectors bound to different
receptors and could therefore behave differently when placed into brain tissues."
Subtle differences in the protein coats of the AAV-based vectors give them
distinct properties, Davidson said.
"In the present study, we found surprising characteristics in AAV5,
one of the AAV-based vectors tested," she said. "The AAV5 had a
unique ability to spread very far beyond the injection site after being introduced
into the brain."
Davidson said the data are exciting because they suggest that AAV5-based
vectors could be used to deliver correct copies of genes to cells throughout
the central nervous system without the need for multiple injections.
The next step is to test the AAV5 vector in animal models of neurodegenerative
diseases. For these studies, DNA sequences encoding therapeutic molecules
will be placed into the AAV5 vectors.
The AAV5 type might eventually have particular application for gene therapy
treatment of disorders where a large proportion of the brain is affected,
such as Alzheimer's disease, Huntington's disease and lysosomal storage diseases
such as Batten disease (a neurodegenerative disease with childhood onset).
In addition to Davidson, Colleen S. Stein, Ph.D., postdoctoral fellow in
Davidon's laboratory, was also a major contributor to the work. John A. Chiorini,
Ph.D., a researcher in the Gene Therapy and Therapeutics Branch of the National
Institute of Dental and Craniofacial Research at the NIH, also collaborated
on the study.
The study was supported in part by an NIH grant. Davidson is also a fellow
of the Roy J. Carver Trust.
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.
NOTE TO EDITORS: Copies of the journal article can be downloaded from the
PNAS website at http://www.pnas.org/cgi/content/full/050581197