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Chronic Anemia Cured by Gene Therapy Using Genetically Engineered Blood Vessels

By BiotechDaily International staff writers
Posted on 29 Nov 2011
A novel gene therapeutic method employing genetically engineered blood vessels to deliver erythropoietin (EPO) to anemic mice was described in a proof-of-concept study.

Investigators at Harvard Medical School (Boston, MA, USA) created a new type of blood vessel by isolating endothelial colony-forming cells from human blood and then inserting into these cells the gene that encodes EPO. The gene that was inserted was part of a complex that included an “off/on switch” activated by the drug doxycycline.

The genetically engineered colony-forming cells were injected under the skin of immunodeficient mice that had been rendered anemic by radiation treatment (as often occurs in cancer patients) or through loss of kidney tissue (modeling chronic kidney failure).

Results published in the November 17, 2011, issue of the journal Blood revealed that the transplanted cells spontaneously formed networks of blood vessels that became integrated into the animals' own circulatory system. EPO produced by the genetically engineered cells was then released directly into the bloodstream. EPO production could be controlled by administrating or withholding doxycycline.

“Blood-vessel implants are an ideal platform technology for gene therapy applications whose goal is systemic drug delivery,” said senior author Dr. Juan M. Melero-Martin, assistant professor of surgery at Harvard Medical School. “Blood vessels are one of the few tissues where we have good control over engraftment. Endothelial cells are easily isolated from blood, are good at assembling themselves into blood vessels, and are ideal for releasing compounds into the bloodstream, since they line the blood vessels.”

“Such drugs are currently made in bioreactors by engineered cells, and are very expensive to make in large amounts. The paradigm shift here is, why we do not instruct your own cells to be the factory?” said Dr. Melero-Martin.

If this approach can be applied in humans, it would relieve patients from having to receive frequent EPO injections, thus reducing the medical costs associated with the management of anemia.

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