September 04, 2008

Safe and Effective small interfering RNA Delivery allows for drugs to be developed in Weeks


Tobacco mosaic virus is like a 18-nanometer wide straw, which can hold gene silencing RNA

The tobacco mosaic virus appears to be the key to safe and effective delivery of gene silencing RNA.

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.”

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.

Protecting the payload is not the only challenge, said Ben Berkhout, a biotechnology expert at the University of Amsterdam. Even if the delicate molecules are packaged in the perfect substance, they still need some sort of a guidance system.

"You want to efficiently get the siRNA drug into the cells where the therapeutic action should be,” said Berkhout.

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.

If that trick works, tobacco may finally be able to turn over a new leaf.



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