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Release: March 20, 2000

UI researchers find potential way to improve gene therapy delivery to brain

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