Researchers Make Key Discovery For Body To Accept Gene Therapy

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Researchers Make Key Discovery For Body To Accept Gene Therapy

http://www.medicalnewstoday.com/articles/131878.php

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. Brink's went to work on a solution,

with an idea brought to them by team member , 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. "