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"Vigilant Vector" Could Insert Genes That Sense, Prevent Heart Attacks

Date:
April 12, 2002
Source:
University Of Florida
Summary:
A team of University of Florida researchers has used gene therapy to develop a tiny biological machine that could one day be injected into heart attack-prone patients to recognize and stop new heart attacks.

GAINESVILLE, Fla. --- A team of University of Florida researchers has used gene therapy to develop a tiny biological machine that could one day be injected into heart attack-prone patients to recognize and stop new heart attacks.

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The UF team used a harmless virus to deliver a combination of genes to animal heart tissue that protected the tissue from heart attacks, according to an article in the February issue of Hypertension, a journal of the American Heart Association. The virus sensed when the heart tissue began to experience hypoxia, or oxygen deprivation, and switched on the protective genes, which prevented the damage and scarring, called ischemia, that usually results.

It may take years, but UF researchers say the technique of using such “vigilant vectors” to transmit gene switches could be translated into treatments for a host of other disorders as well, such as diabetes and stroke.

“The concept is that we give an IV injection, and although the vector goes everywhere in the body, it only works in the heart or other targeted organ or tissue” said Ian Phillips, the study’s principal investigator and a professor and chairman emeritus of the UF College of Medicine’s department of physiology. “It just waits there until the right moment arrives to help the person.”

Other researchers have used so-called “antisense” genes to prevent high blood pressure. The UF team applied the same concept to heart attacks, said Phillips, who also is an associate vice president of research and graduate programs at UF.

One out of every five people, or nearly 62 million Americans, suffer from some form of cardiovascular disease, according to the American Heart Association. It has been the No. 1 killer of Americans nearly every year since 1900. At least 12.6 million of those suffer from coronary heart disease, the type of cardiovascular disease the UF research addresses.

The UF team used the adeno-associated virus, a commonly used gene carrier, to insert the cardio-protective gene switch. The approach is a classic example of “bionanotechnology,” or manipulating basic elements of biology such as DNA and proteins for research and therapeutic purposes, Phillips said.

UF researchers pioneered the use of adeno-associated virus, or AAV, for gene therapy. The apparently harmless virus has unusual properties that make it ideal for transporting corrective genes into human cells, including that it carries no DNA of its own, Phillips said.

The UF team spent two years developing the heart-attack-preventing gene “switch” using a combination of genes from human and yeast cells, Phillips said.

Active only in heart tissue, the switch “turns on” the protective genes during the four- to six-hour window when hypoxia is known to lead to ischemia. This defends the heart cells in the low oxygen condition and subsequently prevents damage to the heart tissue, Phillips said. When the hypoxia goes away, the switch turns off again.

The research has so far proved successful in animal tissue cultures and on a limited basis in experiments with live rats, but Phillips said developing experiments and treatment for people is still many years away. The researchers used components derived from yeast cells to increase production of the gene switch 300-fold, which is important because large amounts of the genes are needed to reduce the effects of ischemia, Phillips said.

No gene therapy treatment using the AAV virus has been approved for use in humans, but there are clinical trials under way for diseases including cystic fibrosis. Phillips said once one treatment is approved, others should follow more easily, since the method remains the same for multiple treatments.

“If you have a new use for a drug already in the market, it’s much easier than getting a new drug into the market,” he said. “The same will be true with the AAV virus.”

That said, the early success with the heart vector research raises the possibility of similar vigilant vectors for other maladies, Phillips said.

For example, it’s possible that a DNA switch could be created to treat diabetes, in which the switch would prompt cells to increase insulin production when it senses that glucose levels in the body are falling. Similar vectors also could protect against strokes and cancer and even against toxins, such as the anthrax toxin, he said.


Story Source:

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


Cite This Page:

University Of Florida. ""Vigilant Vector" Could Insert Genes That Sense, Prevent Heart Attacks." ScienceDaily. ScienceDaily, 12 April 2002. <www.sciencedaily.com/releases/2002/04/020412074854.htm>.
University Of Florida. (2002, April 12). "Vigilant Vector" Could Insert Genes That Sense, Prevent Heart Attacks. ScienceDaily. Retrieved November 22, 2014 from www.sciencedaily.com/releases/2002/04/020412074854.htm
University Of Florida. ""Vigilant Vector" Could Insert Genes That Sense, Prevent Heart Attacks." ScienceDaily. www.sciencedaily.com/releases/2002/04/020412074854.htm (accessed November 22, 2014).

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