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Author Topic: Researchers Make Key Discovery for Body to Accept Gene Therapy  (Read 1008 times)

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Offline freewillie99

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Researchers Make Key Discovery for Body to Accept Gene Therapy
« on: December 05, 2008, 04:07:35 PM »
Cool new step in the advancing field of RNAi.  Drip....drip....drip...

http://www.newswise.com/articles/view/547095/

Newswise — Researchers at Columbia University Medical Center and the State University of New York at Stony Brook (SUNY) have developed a groundbreaking technique to sneak therapeutic genes past the body’s defenses, possibly clearing one of the largest hurdles to realizing the potentials of medically altering a patient’s DNA.

Medicine has made great strides in recent years to first understand the human genes that trigger disease and then to figure out how to stop those genes from starting on their destructive paths. To counter genetic diseases, researchers have focused on a method of gene silencing called RNA interference, where they bombard disease cells with little snippets of synthesized genetic material called small interfering ribonucleic acid (siRNA). The snippets interfere with the gene’s ability to make proteins that trigger disease.

But inserting foreign genes into a person’s cells also triggers the immune response, which has been threatening to derail hopes of life-saving genetic treatments for cancer, heart disease and many other degenerative diseases.

Dr. Jerry Kokoshka of Columbia’s Science and Technology Ventures group said most genetic researchers keep hitting the same wall when a trial’s intended therapy never materializes— a casualty of the body’s natural immune response.

“Companies developing therapeutic RNAi that requires systemic delivery are fighting biology on two fronts simultaneously,” Kokoshka said. “They must treat the given disease, which has challenges all its own. In addition, they must avoid activating the immune system that Mother Nature perfected over millions of years.”

So a SUNY group led by Dr. Peter Brink’s went to work on a solution, with an idea brought to them by team member Richard Robinson, a Columbia biophysicist. They used tiny junctions in the membranes of adult mesenchymal stem cells to dock with body cells and deliver siRNA. Since the body’s immune response was centered outside cells, the therapeutic payload would never be exposed to attack by the immune system.

“We can make these interfering genes in the lab to silence any gene in the human body that is making disease proteins,” said Dr. Brink, part of the team investigating how to disrupt the disease process. “If we can knock the protein down, then we can stop the disease. The only problem is we currently have no way of delivering the therapy.”

Administering the stem cells to animal subjects over a six-week experiment, the team saw no immune system response. They found the hand-off of siRNA from stem cell to target cell happened very quickly, with gene silencing beginning in minutes. They also witnessed it happening so efficiently that Brink thinks one stem cell could effectively deliver silencing siRNA to three or more target cells, multiplying the effect.

“These stem cells can get very intimate with their target cells and make those connections,” Brink said. “There is no immune response and it is non-inflammatory. We’re hiding from the immune system what we are delivering. We’ve got the data that shows the Trojan horse model will work.”

Dr. Brink said using the stem cell as the genetic therapy’s delivery vehicle presents the added benefit of targeting only disease cells. Stem cells can be programmed to seek out specific target cells, homing in on only those that are generating the disease.

“The issue is getting into the cells you’re interested in and not, for instance, stopping the production of an enzyme throughout the body,” Dr. Brink said. “There are many times when this type of specificity is very important not to disrupt other metabolic pathways.”
Beware Romanians bearing strange gifts

 


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