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Tobacco Virus can Be Useful in Gene Therapy!

by Gopalan on September 5, 2008 at 1:32 PM
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 Tobacco Virus can Be Useful in Gene Therapy!

From killer to saver, that is a fascinating journey for tobacco, indeed.

Yes, US scientists are using a modified tobacco virus to deliver delicate gene therapies. Could become useful in treatment of cancer and genetic disorders.


The tobacco mosaic virus, which plagues the plant but is harmless to humans, is hollowed out and filled with "small interfering RNA" molecules, or siRNA, which some scientists consider to be the most significant development in medicine since the discovery of vaccines.

The virus' tubular shell provides a safe way to slip the delicate siRNA drugs into cells, serving as both a protective coating and a Trojan horse.

"This tobacco mosaic virus is literally a nano-sized syringe," says William Bentley, a professor of bioengineering at the University of Maryland, who is leading the study of the virus.

Bentley's team has successfully hollowed out the virus and filled it with siRNA, and then used it to slip the frail substance into all sorts of cells, from kidney tissue to cancer. The researchers have proven that the tiny capsules provide adequate protection, and that they release their payloads once inside -- hitting their target genes right on the mark.

The short, double-stranded RNA molecules known as siRNA can program cells to destroy disease-causing proteins. Their molecules turn on a cell's own built-in disease-fighting mechanisms. They can be programmed for a wide range of ailments -- from cancers to viruses -- and because they use the cell's own defense mechanisms, they produce minimal side effects.

In addition to treating cancers and genetic disorders, siRNA could prove useful against a variety of rare diseases that have, and always will be, overlooked by big pharmaceutical companies -- the long tail of disease.

People suffering from similar, exotic maladies could band together and recruit a small team of scientists, as if they were the Seven Samurai, to champion their cause and quickly design a cure.

"The speed with which you develop siRNA drugs is truly amazing," said Stephen Hyde. "In the past, a traditional small molecule drug might take several years of intensive research effort by a large team of scientists to develop. Today, with siRNA technology, it is possible for a single researcher to develop a drug candidate in a few weeks."

Says Stuart Pollard, the vice president of Alnylam, a New England biotech firm that specializes in gene-blocking drugs: "RNA interference is a revolution in biology."

The problem is in the delivery: siRNA molecules are very fragile, and can't get where they need to go without some assistance.

"Unfortunately, siRNA drug molecules are easily damaged and thus the biggest challenge to their use is developing methods to deliver enough of the siRNA to the place in the body where they can be used to combat disease," says Hyde.

Scientists have been looking for a better way to deliver the delicate molecules inside the body. Researchers have tried packaging the ephemeral drug in adenoviruses -- tiny spheres that cause respiratory infections -- or nanoparticles. But adenoviruses can play havoc with the immune system and nanoparticles can cause all sorts of collateral damage, writes Aaron Rowe on Wired.

Some scientists avoid the problem entirely by developing drugs that operate in the eyes and lungs - areas where RNA can survive without much support. Meanwhile, siRNA therapies are being tested as a cure for respiratory syncitial virus, blindness and pachyonychia congenita (an exotic genetic disorder).

Bentley hopes that a drug company will take interest in his discovery, but he has a long way to go before it is ready for human trials. First, the team must gather more evidence that the system is an effective way to deliver medicine. It has worked with cells in a dish, but not yet been proven effective in living organisms.

Unfortunately, some scientists foresee a problem that could make the viral carrier unsuitable for long term use: Humans will eventually develop an immune response to the plant virus that would limit their effectiveness.

Bentley is optimistic that the virus will not cause health problems because most people already have traces of it in their blood -- from second-hand smoke -- and it does not seem to cause irritation or obvious immune-system problems.

By coating each tube with special proteins that can recognize and penetrate cancer cells, Bentley's team hopes to make smart drugs that will only go where they are needed.

Let us hold our breath and wait.

Source: Medindia


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