Featured Research

from universities, journals, and other organizations

Study Shows Receptor Molecule Facilitates Introduction Of Corrected Genes Into Cells

Date:
June 1, 2000
Source:
University Of North Carolina At Chapel Hill
Summary:
Medical researchers trying to perfect gene therapy face a major obstacle in inserting corrected genes into cell nuclei where they can direct production of healthy proteins that the defective cellular machinery cannot make. Now, University of North Carolina at Chapel Hill School of Medicine scientists have found what they think could be a big improvement. For the first time, they have targeted a special class of receptor molecules on the surfaces of airway cells.

Medical researchers trying to perfect gene therapy face a major obstacle in inserting corrected genes into cell nuclei where they can direct production of healthy proteins that the defective cellular machinery cannot make.

In the past, scientists have used weakened viruses as vectors to carry working genes into cells, but so far the body's sophisticated natural defenses against invaders -- especially in the lung -- have limited their effectiveness.

Now, University of North Carolina at Chapel Hill School of Medicine scientists have found what they think could be a big improvement. For the first time, they have targeted a special class of receptor molecules on the surfaces of airway cells. Their experiments show that when activated, a G-protein-coupled receptor can work like a revolving door allowing weakened viruses into cells, along with their attached therapeutic payload.

A report on the research appears in the June issue of Nature Biotechnology. Authors are Drs. Silvia M. Kreda, Raymond J. Pickles and Eduardo R. Lazarowski, all research associates in medicine, and Dr. Richard C. Boucher, Kenan professor of medicine.

"We linked an adenovirus vector to a small signaling molecule known as UTP that interacts with the receptor, and we obtained specific gene transfer in human airway cells," Kreda said. "This strategy is flexible and conceptually could allow us to successfully correct other cell types or use different gene therapy vectors."

Boucher, director of UNC-CH's Cystic Fibrosis Center, likened vectors to mail delivery trucks moving valuable cargo. He also called the strategy "the classic Trojan Horse approach" because it tricks the mostly impenetrable cell surfaces. Their success sets the stage for developing a system with clinical applications.

"You have to make the virus look like something else that can attach to airway cells and have the capacity to penetrate inside," he said. "Dr. Kreda's paper shows there actually are these receptors on the side of cells facing the airways and that if you can dress up viruses with UTP, you can fool the cells into opening their doors long enough for the virus to sneak in."

The scientists are now attempting to boost the vector's efficiency in entering cells, Boucher said. After that, they will try to correct defective cystic fibrosis cells in tissue culture, in mouse models of cystic fibrosis pioneered at UNC-CH and, eventually, in human volunteers.

"All of us are very keen to the notion that you have to be careful and very safe when attempting gene therapy studies in humans," he said. "It's only when people try to rush ahead and cut corners do problems arise."

Common on the airway side of cells lining the lungs, the G-protein-coupled receptor the UNC-CH team targets is a purinergic receptor known as P2Y2, Kreda said. Scientists want to correct the CFTR gene, which malfunctions in people with cystic fibrosis, so patients' lungs can maintain the proper balance of salt and water. Otherwise, lung secretions become too thick and sticky, resulting in a series of debilitating infections and premature death.

In the current study, she and colleagues did not transfer the cystic fibrosis gene but instead used "reporter" genes, which are easier to measure inside cells using fluorescent technology and enzymatic activity levels.

"This is exciting and we think very promising and important because we were able to break one of the barriers epithelial cells offer to viral vectors," Kreda said.

The National Institutes of Health and the Cystic Fibrosis Foundation supported the continuing research.


Story Source:

The above story is based on materials provided by University Of North Carolina At Chapel Hill. Note: Materials may be edited for content and length.


Cite This Page:

University Of North Carolina At Chapel Hill. "Study Shows Receptor Molecule Facilitates Introduction Of Corrected Genes Into Cells." ScienceDaily. ScienceDaily, 1 June 2000. <www.sciencedaily.com/releases/2000/05/000531071132.htm>.
University Of North Carolina At Chapel Hill. (2000, June 1). Study Shows Receptor Molecule Facilitates Introduction Of Corrected Genes Into Cells. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2000/05/000531071132.htm
University Of North Carolina At Chapel Hill. "Study Shows Receptor Molecule Facilitates Introduction Of Corrected Genes Into Cells." ScienceDaily. www.sciencedaily.com/releases/2000/05/000531071132.htm (accessed August 28, 2014).

Share This




More Health & Medicine News

Thursday, August 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Killer Amoeba Found in Louisiana Water System

Killer Amoeba Found in Louisiana Water System

AP (Aug. 28, 2014) State health officials say testing has confirmed the presence of a killer amoeba in a water system serving three St. John the Baptist Parish towns. (Aug. 28) Video provided by AP
Powered by NewsLook.com
Who Could Be Burnt by WHO's E-Cigs Move?

Who Could Be Burnt by WHO's E-Cigs Move?

Reuters - Business Video Online (Aug. 28, 2014) The World Health Organisation has called for the regulation of electronic cigarettes as both tobacco and medical products. Ciara Lee looks at the impact of the move on the tobacco industry. Video provided by Reuters
Powered by NewsLook.com
CDC Director On Ebola Outbreak: 'It's Worse Than I Feared'

CDC Director On Ebola Outbreak: 'It's Worse Than I Feared'

Newsy (Aug. 28, 2014) CDC director Tom Frieden says the Ebola outbreak is even worse than he feared. But he also said there's still hope to contain it. Video provided by Newsy
Powered by NewsLook.com
How A 'Rule Of Thumb' Could Slow Down Drinking

How A 'Rule Of Thumb' Could Slow Down Drinking

Newsy (Aug. 28, 2014) A study suggests people who follow a "rule of thumb" when pouring wine dispense less than those who don't have a particular amount in mind. 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