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Borrowing from Ebola virus could aid cystic fibrosis gene therapy

A problem with current efforts in developing a cystic fibrosis gene therapy is that delivering genes into airway cells is inefficient and requires disrupting the integrity of the cell layer. However, a finding by University of Iowa researchers and colleagues may help solve the problem by using a surprising tool -- a modified piece of the Ebola virus. The findings will appear in issue 10 (May) of the Journal of Virology.

The investigators found that taking a small part of the protein coat from the Ebola virus and putting it on another modified virus creates a hybrid vehicle that can attach itself to a receptor on the top surface, or airway side, of lung cells. The genes within the vehicle can then enter the host cell, where they integrate into the host chromosomes. Previously studied gene delivery vehicles can attach only to the bottom surface, which requires breaching the normally closed cell surface layer.

The discovery has implications for treating cystic fibrosis and other lung conditions where the genes needed for healthy lung function are mutated or absent.

"Most people understandably do not think of the Ebola virus in a favorable light, but our approach takes a small part from this bad virus and puts it in a hybrid system to get some good out it," said Paul McCray, M.D., UI professor of pediatrics and lead investigator of the study.

"A large region of the Ebola protein coat, or envelope, is deleted, so it is potentially safer to use," said Patrick Sinn, Ph.D., a UI post-doctoral fellow in pediatrics and the paper's lead author.

The investigation was done in healthy human airway cells that functionally mimic actual human airways. Clinical applications of the finding are only potential at this time.

"We still are multiple steps from knowing whether this Ebola-modified vector can deliver therapeutic genes into the airway cells of people with cystic fibrosis and correct the genetic defect," McCray cautioned. "Howev
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Contact: Becky Soglin
becky-soglin@uiowa.edu
319-335-6660
University of Iowa
30-Apr-2003


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