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Gene Therapy Versus Atherosclerosis

Via EurekAlert!, news of a promising study in rabbits: "A one-dose method for delivering gene therapy into an arterial wall effectively protects the artery from developing atherosclerosis despite ongoing high blood cholesterol. ... As applied in our study, the introduced genes can produce proteins that counteract the fundamental processes that drive atherosclerosis, including preventing lipid accumulation inside the artery wall and decreasing recruitment of inflammatory cells. We found both of these effects. ... Gene transfer would move the production of the therapeutic 'drug' (in this case a therapeutic gene) directly to the site of atherosclerosis development: the blood vessel wall. The approach maximizes delivery of the drug to the artery wall and minimizes side effects in the rest of the body. ... The deployed gene produces a protein that is likely responsible for the beneficial effects of high-density lipoprotein, or HDL, commonly known as good cholesterol. This substance is apolipoprotein A-1, or apoA-1. It pumps out harmful cholesterol from the scavenger-type cells that ingest fats and congregate in early atherosclerotic lesions. ApoA-1 appears to remove cholesterol from the lesions and is capable of transporting it to the liver, where it can be excreted from the body. Lack of a suitable vector to transfer apoA-1-manufacturing genes into the cells lining the arterial wall has hampered the progress of this approach. Normally apoA-1 is produced by cells in the liver, stomach and intestine and enters the artery wall only after circulating through the blood. [The] researchers successfully used a helper-dependent adenovirus (HDAd) as the vehicle to transfer a genomic clone of rabbit apo-A1 into the carotid artery. This large blood vessel sends oxygenated blood to the brain. After the vector was infused into the artery, the gene was taken up almost exclusively by the cells in the thin layer that lines the carotid's inner surface and is in contact with circulating blood."

Link: http://www.eurekalert.org/pub_releases/2011-07/uow-gtd071911.php

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