Wednesday, September 3, 2008

Tobacco Could Hold the Key to Revolutionary Gene Therapy

By Aaron Rowe EmailSeptember 03, 2008 | 4:43:36 PMCategories: BiotechnologyChem LabChemistryGene TherapyNanotechnology  










“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.

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).

In a recent clinical trial, Alnylam packed siRNA into a nasal inhaler and found the spray cut in half the number of patients who were infected with respiratory syncitial virus. Even better, the drug had no side effects. It was comparable to a saltwater placebo.

A lucky coincidence led Bentley and his team at the University of Maryland to use the tobacco mosaic virus as a delivery mechanism. 

His lab is across the hall from the office of James Culver, a biotechnology expert who had been using the virus to produce nano wires and batteries.

Bentley's team can produce boatloads of the plant pathogen, empty it out and cram siRNA into the hollow core. 

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.




