Nav: Home

Targeting Gene Therapy To Specific Cells: Technique Opens Door To Prevention Of Restenosis After Angioplasty

August 26, 1997

Researchers at the University of Chicago Medical Center have developed the first practical method to restrict the activity of genes used for gene therapy to a specific cell type. This discovery, made in animals, neatly sidesteps one of the chief safety hurdles slowing the advance of gene therapy in humans.

By attaching a recently discovered "on-off" switch for gene expression, taken from a gene that is turned on only in smooth muscle cells -- which play a crucial role in cardiovascular disease -- the researchers were able to restrict the action of the inserted genes to that specific cell type.

The research, which used a specially prepared virus to insert the marker genes into animal models, is reported in the September 1 issue of the Journal of Clinical Investigation.

"The ability to direct a gene to a specific cell type and prevent expression in other cell types is a powerful new tool that allows us to bypass one of the most troubling safety concerns facing gene therapy," said Michael Parmacek, M.D., assistant professor of medicine at the University of Chicago and director of the study. "For the first time, we can use a virus to insert a therapeutic gene into smooth muscle cells in the body without worrying about its potential effects on other tissues, such as the lungs or liver."

Most current gene therapy approaches rely on cold viruses, crippled so that they can't multiply within the body, to insert copies of potentially therapeutic genes into cells. While these viruses are extremely efficient, they infect many different cell types, making it difficult to direct new genes to only one.

But by placing the gene under the control of a "promoter" -- an on-off switch for gene expression -- from a gene (SM22a) that is expressed only in smooth muscle cells, Parmacek's team found that no matter which types of cells were infected, the gene was only "turned on" in smooth muscle cells.

Remarkably, no matter how the researchers injected the custom-made gene-delivery virus -- whether into an artery, intravenously or directly into muscle -- gene expression was limited to the targeted cells. T

he finding suggests that other promoters could restrict expression to other cell types.

"If we, as cardiologists, had to choose one cell type to start with, this would be our first choice," said Parmacek.

Smooth muscle cells surround blood vessels, regulating how they contract and expand. The proliferation of smooth muscle cells after a vessel injury is a major contributor to atherosclerosis and is the leading cause of re-blockage of arteries after angioplasty.

In 1995, University of Chicago researchers demonstrated that gene therapy, using a virus, could be used to combat restenosis following angioplasty in several animal models. (Published in Science, 27 January 1995)

"But until now, we hesitated to use these therapeutic viruses in humans due to our concern that they would indiscriminatly infect all cells," said Parmacek. "The use of the SM22a promoter to target recombinant gene expression specifically to arterial smooth muscle cells alleviates many of our safety concerns and clears the path to human trials."

Smooth muscle cells also modulate airway resistance, a key factor in asthma, and gut motility, important in irritable bowel syndrome. Targeted gene therapy, which would affect smooth muscle cells but not skeletal muscle, holds promise for treatment of these and other disorders.

Other members of the research team included Steven Kim, Hua Lin, Eliav Barr, Lien Chu and Jeffrey Leiden of the departments of medicine and pathology at the University of Chicago. The research was supported by grants from the Public Health Service and the Falk Charitable Trust.

University of Chicago Medical Center

Related Cardiovascular Disease Articles:

New insights into the effect of aging on cardiovascular disease
Aging adults are more likely to have - and die from - cardiovascular disease than their younger counterparts.
Premature death from cardiovascular disease
National data were used to examine changes from 2000 to 2015 in premature death (ages 25 to 64) from cardiovascular disease in the United States.
Ultrasound: The potential power for cardiovascular disease therapy
In the current issue of Cardiovascular Innovations and Applications volume 4, issue 2, pp.
Despite the ACA, millions of Americans with cardiovascular disease still can't get care
Cardiovascular disease (CVD) is the leading cause of death for Americans, yet millions with CVD or cardiovascular risk factors (CVRF) still can't access the care they need, even years after the implementation of the Affordable Care Act (ACA).
Excess weight and body fat cause cardiovascular disease
In the first Mendelian randomization study to look at this, researchers have found evidence that excess weight and body fat cause a range of heart and blood vessel diseases (rather than just being associated with it).
Disease remission associated with 80% reduction in risk of cardiovascular outcomes
The results of a study presented today at the Annual European Congress of Rheumatology (EULAR 2019) demonstrate that remission in patients with rheumatoid arthritis is associated with an 80% reduction in risk of cardiovascular outcomes.
Enzyme may indicate predisposition to cardiovascular disease
Study suggests that people with low levels of PDIA1 in blood plasma may be at high risk of thrombosis; this group also investigated PDIA1's specific interactions in cancer.
Cardiovascular disease in China
This study analyzed data from the Global Burden of Disease Study to look at the rate of cardiovascular disease (CVD) in China along with death and disability from CVD from 1990 to 2016.
Obstructive sleep apnea and cardiovascular disease in women
Obstructive Sleep Apnea and Cardiovascular Disease in Women In the current issue of Cardiovascular Innovations and Applications (Special Issue on Women's Cardiovascular Health, Volume 3, Number 4, 2019, Guest Editor Gladys P.
Nearly half of all adult Americans have cardiovascular disease
At least 48 percent of all adults in the United States have some form of cardiovascular disease, according to the latest statistics provided by the American Heart Association.
More Cardiovascular Disease News and Cardiovascular Disease Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Uncharted
There's so much we've yet to explore–from outer space to the deep ocean to our own brains. This hour, Manoush goes on a journey through those uncharted places, led by TED Science Curator David Biello.
Now Playing: Science for the People

#555 Coronavirus
It's everywhere, and it felt disingenuous for us here at Science for the People to avoid it, so here is our episode on Coronavirus. It's ok to give this one a skip if this isn't what you want to listen to right now. Check out the links below for other great podcasts mentioned in the intro. Host Rachelle Saunders gets us up to date on what the Coronavirus is, how it spreads, and what we know and don't know with Dr Jason Kindrachuk, Assistant Professor in the Department of Medical Microbiology and infectious diseases at the University of Manitoba. And...
Now Playing: Radiolab

Dispatch 1: Numbers
In a recent Radiolab group huddle, with coronavirus unraveling around us, the team found themselves grappling with all the numbers connected to COVID-19. Our new found 6 foot bubbles of personal space. Three percent mortality rate (or 1, or 2, or 4). 7,000 cases (now, much much more). So in the wake of that meeting, we reflect on the onslaught of numbers - what they reveal, and what they hide.  Support Radiolab today at Radiolab.org/donate.