Featured Research

from universities, journals, and other organizations

Iowa Researchers: Step Made In Developing Gene Therapy To Treat Cystic Fibrosis

Date:
December 2, 1999
Source:
University Of Iowa
Summary:
A team of University of Iowa Health Care investigators has advanced understanding of how gene therapy might effectively treat the serious lung function loss associated with cystic fibrosis (CF). Some basic problems have thwarted one gene therapy treatment approach which involves using a vector -- a disabled virus or other carrier -- to insert working copies of a specific mutated gene into an affected person's lung cells.

NOTE TO EDITORS: This news release refers to a journal article which can be accessed at http://www.jci.org/cgi/content/full/199908390 .

IOWA CITY, Iowa -- A team of University of Iowa Health Care investigators has advanced understanding of how gene therapy might effectively treat the serious lung function loss associated with cystic fibrosis (CF). Some basic problems have thwarted one gene therapy treatment approach which involves using a vector -- a disabled virus or other carrier -- to insert working copies of a specific mutated gene into an affected person's lung cells.

"The UI study addressed two fundamental problems currently preventing progress of gene therapy for cystic fibrosis -- inefficient gene transfer and lack of gene persistence," said Paul McCray, M.D., UI associate professor of pediatrics and co-principal investigator. The team used human cell cultures and in vivo, or animal, models to demonstrate both efficient and lasting gene transfer into airway cells.

The investigators demonstrated functional gene activity that lasted six months in the human cells in culture and six weeks in the rabbits' airways. The findings were published online Nov. 24 by the Journal of Clinical Investigation. The print version will be published Dec. 6.

"This is another incremental step toward figuring out how we might apply gene therapy to treat cystic fibrosis," McCray said. "Our findings could lead to new approaches for future CF gene therapy trials."

People with CF have serious lung and digestive problems due to malfunctioning ion channels that normally regulate salt and water secretions to protect the lungs. A specialized protein called the CF transmembrane conductance regulator (CFTR) makes the channel. However, in people with CF, the gene that codes for the CFTR protein is mutated.

Previous research, including a 1998 study McCray led using human cell cultures, demonstrated that a vector, which carries a working copy of the mutated gene, can more effectively enter a cell if it is mixed with a calcium chelator. The chelator binds with calcium to disrupt tight junctions between the cells. The vector can then reach cell receptors and transduce the cell -- cross its surface and deposit the gene.

In the most recent study, McCray's team used a new vector from the retrovirus family, feline immunodeficiency virus (FIV), which causes leukemia in cats but causes no disease in humans. Chiron Technologies in San Diego created the FIV-based retrovirus.

"We saw in both human cell cultures and in rabbits that FIV vectors will transduce, or infect, nondividing cells, which eliminates the need to stimulate cell division to get the vector to work," McCray said. "This is very important because normally very few lung cells are dividing."

McCray said the method of using a calcium chelator-enhanced vector to bolster a vector's ability to transduce cells could be used in a human trial to increase gene transfer efficiency.

"The principle applies to three classes of vectors that investigators use to study gene transfer for cystic fibrosis -- retrovirus, adenovirus and adeno-associated viruses," he said.

The UI study was also significant in its findings on gene persistence, McCray added. The researchers found that the gene transferred by the FIV vector into human airway cells in culture continued to show functional CFTR activity for up to six months. In contrast, the effectiveness of an adenovirus vector wore off after about three weeks. FIV-transduced gene expression in the airway cells of live rabbits lasted six weeks (the duration of the study).

"We think the CFTR gene persists because the FIV vector allows it into the chromosomes of lung cells with the potential to divide and pass the gene on to their daughter cells," McCray said. "Unlike nonviral carriers or an adenovirus, a retrovirus such as FIV has this ability."

In addition to McCray, UI investigators included Beverly Davidson, Ph.D., associate professor of internal medicine and director of the Gene Transfer Vector Core; Guoshun Wang, Ph.D., research scientist in pediatrics; and Joseph Zabner, M.D., assistant professor of internal medicine.

The UI study was funded by grants from the Cystic Fibrosis Foundation, the National Institutes of Health, and the Children's Miracle Network telethon. McCray also received a Career Investigator Award from the American Lung Association. Davidson and Zabner are Fellows of the Roy J. Carver Charitable Trust.

Cystic fibrosis is the most common fatal hereditary disease in the United States. According to the Cystic Fibrosis Foundation, CF affects approximately 30,000 children and adults in the United States. The disease occurs in approximately one of every 3,300 live births and is usually diagnosed in early childhood. Lung function loss due to chronic infection is the most common cause of the shortened life expectancy of people with CF.

###

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.


Story Source:

The above story is based on materials provided by University Of Iowa. Note: Materials may be edited for content and length.


Cite This Page:

University Of Iowa. "Iowa Researchers: Step Made In Developing Gene Therapy To Treat Cystic Fibrosis." ScienceDaily. ScienceDaily, 2 December 1999. <www.sciencedaily.com/releases/1999/12/991202070208.htm>.
University Of Iowa. (1999, December 2). Iowa Researchers: Step Made In Developing Gene Therapy To Treat Cystic Fibrosis. ScienceDaily. Retrieved August 20, 2014 from www.sciencedaily.com/releases/1999/12/991202070208.htm
University Of Iowa. "Iowa Researchers: Step Made In Developing Gene Therapy To Treat Cystic Fibrosis." ScienceDaily. www.sciencedaily.com/releases/1999/12/991202070208.htm (accessed August 20, 2014).

Share This




More Health & Medicine News

Wednesday, August 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola-Hit Sierra Leone's Freetown a City on Edge

Ebola-Hit Sierra Leone's Freetown a City on Edge

AFP (Aug. 19, 2014) Residents of Sierra Leone's capital voice their fears as the Ebola virus sweeps through west Africa. Duration: 00:56 Video provided by AFP
Powered by NewsLook.com
101-Year-Old Working Man Has All The Advice You Need

101-Year-Old Working Man Has All The Advice You Need

Newsy (Aug. 19, 2014) Herman Goldman has worked at the same lighting store for almost 75 years. Find out his secrets to a happy, productive life. Video provided by Newsy
Powered by NewsLook.com
Researcher Testing on-Field Concussion Scanners

Researcher Testing on-Field Concussion Scanners

AP (Aug. 19, 2014) Four Texas high school football programs are trying out an experimental system designed to diagnose concussions on the field. The technology is in response to growing concern over head trauma in America's most watched sport. (Aug. 19) Video provided by AP
Powered by NewsLook.com
American Ebola Patient Apparently Improving, Outbreak Is Not

American Ebola Patient Apparently Improving, Outbreak Is Not

Newsy (Aug. 19, 2014) Nancy Writebol, an American missionary who contracted Ebola, is apparently getting better, according to her husband. The outbreak, however, is not. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins