Featured Research

from universities, journals, and other organizations

One Dose Of 'Designer' Gene Therapy May Target Specific Body Area

Date:
January 20, 2004
Source:
American Heart Association
Summary:
Doctors may soon be able to inject gene therapy intravenously that travels to a specific part of the body, according to a study published in Circulation: Journal of the American Heart Association.

DALLAS, Jan. 20 – Doctors may soon be able to inject gene therapy intravenously that travels to a specific part of the body, according to a study published in today's rapid access issue of Circulation: Journal of the American Heart Association.

"It may be possible to design and construct genetically engineered 'designer' gene therapy for selectively delivering genes to any part of the body," said Andrew H. Baker, Ph.D., lead investigator of the study and a reader in molecular medicine at the University of Glasgow in Scotland. "We can't do that now because much of what's injected would be sequestered by the liver." The liver cleanses the blood of foreign material, among other functions.

Gene therapy involves inserting the treatment genes into a virus that is either harmless to humans or has had its disease-causing component removed. The virus is then injected or inserted into the body where it "infects" an area with gene therapy.

Baker's team redesigned a virus called adeno-associated virus (AAV) so that it is not quarantined by the liver, but rather remained in the bloodstream long enough to "infect" specific cells in the body -- in this case, the vascular endothelial cells (ECs). The new therapy targets vascular endothelial cells, which line the inside of blood vessels.

"Vascular endothelial cells, which are in continuous contact with the bloodstream and integrally involved in cardiovascular abnormalities, are appropriate targets for gene therapy," Baker said.

Baker said that AAV is important because it has the potential for long-term gene expression from a single dose. This is based on results from hemophilia studies from other laboratories in which the virus was used to deliver gene therapy. In these studies, Baker said that a single dose could last up to five years, possibly longer as the studies are ongoing. AAV is also a good choice because it does not cause disease in humans.

"The concept of developing systematically injectable gene transfer vehicles is important for a number of potential cardiovascular gene therapies, particularly in those conditions where access to the target site can only realistically be achieved via the bloodstream" he said. "This work shows for the first time that this is possible using cell-specific peptides to modify AAV vehicles for systemic gene delivery.

Researchers modified the virus with two new peptides, or small proteins, that bind specifically to ECs. They inserted these peptides into the virus to create endothelial cell-selective proteins to make, essentially, a designer virus, Baker said.

The peptides are called msl and mtp. The unmodified form of AAV is called the "wild type," or AAVwt. The modified forms of the virus are called AAVmsl and AAVmtp.

Baker and his colleagues studied how the modified viruses interacted with endothelial cells in the laboratory as well as in mice. In laboratory studies, researchers showed that the unmodified virus was 100 times more infective in liver cells than in ECs. The modified virus, however, had more favorable infectivity for vascular ECs, Baker said.

In mouse studies, the modified viruses accumulated at lower levels than the wild type in the major organs, predominantly the liver. Secondly, the modified AAV remained in the blood circulation longer than wild-type AAV, presumably because of reduced liver sequestration. Also, the modified virus accumulated at the target vascular endothelial site.

Baker said that his results could improve the selectivity and efficiency of gene delivery to the cardiovascular system, which could also improve the safety of using it.

Co-authors are Steve D. White, D. Phil.; Stuart A. Nicklin, Ph.D.; Hildegard Bόning, Ph.D.; M. Julia Brosnan, Ph.D.; Kristen Leike; Emmanuel D. Papadakis, B.Sc.; and Michael Hallek, M.D.


Story Source:

The above story is based on materials provided by American Heart Association. Note: Materials may be edited for content and length.


Cite This Page:

American Heart Association. "One Dose Of 'Designer' Gene Therapy May Target Specific Body Area." ScienceDaily. ScienceDaily, 20 January 2004. <www.sciencedaily.com/releases/2004/01/040120034706.htm>.
American Heart Association. (2004, January 20). One Dose Of 'Designer' Gene Therapy May Target Specific Body Area. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2004/01/040120034706.htm
American Heart Association. "One Dose Of 'Designer' Gene Therapy May Target Specific Body Area." ScienceDaily. www.sciencedaily.com/releases/2004/01/040120034706.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