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The UW researchers successfully used a helper-dependent adenovirus(HDAd) as the vehicle to transfer a genomic clone of rabbit apo-A1into the carotid artery. This large blood vessel sends oxygenatedblood to the brain. After the vector was infused into the artery,the gene was taken up almost exclusively by the cells in the thinlayer that lines the carotid's inner surface and is in contact withcirculating blood. At two weeks, atherosclerosis in the carotid artery, as measured bylesion size and lipid content, was minimal and similar in fat-fedrabbits with or without gene therapy. Between weeks two and four,disease measurements increased in control arteries, but were stableor decreased in treated ones. A lengthier study of chow-fed rabbits revealed that apo-A1production from a treated artery continued for at least 48 weeksafter a single dose of gene therapy. The researchers concluded, "HDAd vectors provide for prolonged,stable expression of therapeutic transgenes in the artery wall. Thetransgene's production of apo-A1 in cells lining the artery wallsignificantly retards atherosclerosis." What made this approach continually effective - far longer thanreported for any other gene therapy efforts of this type - were thetype of gene delivery vector and the type of receiving cell. Pastattempts at gene therapy for atherosclerosis delivered to theartery wall were effective for only a few days. Then body's immunesystem recognized and wiped out the foreign protein vector. The HDAd vector, and the production of Apo-1, persisted because,unlike most other vectors, HDAd does not produce any viralproteins. It remains under the radar of the immune system and doesnot provoke serious inflammation. Also, the long-living cells thattook up the gene transfer have very low turnover and proliferationrates. Even if some initial cell loss occurs after vector infusion,most of the cells seem to stay alive at the site of gene therapy,for the duration. Another hopeful experimental finding: This vector didn't set upgene factories in other parts of the body. The vector genome was ator below the limit of detection in multiple samples of differenttissues and organs. Its presence in the artery didn't upset normalblood values. Keeping vectors restricted "on location" can avoidprovoking harmful systemic inflammatory reactions or other unwantedside effects. The researchers plan to test whether HDAd treatment providespersistent protection against atherosclerosis (at least six monthsin fat-fed rabbits) and test whether HDAd can be efficientlydelivered into vein segments before surgically grafting the veinsinto the arterial circulation. Vein grafts are commonly used tobypass blocked heart arteries; however, the effectiveness of veinbypass grafts is limited by rapid development of atherosclerosis. "Vein grafts are an attractive setting for gene therapy becausethey can be treated efficiently and completely after they areremoved from the body and before surgical reimplantation," Dicheksaid. Overall, this week's reported findings suggest that delivering theApoA-1 gene once via the HDAd vector might protect blood vesselsagainst atherosclerosis and potentially provide life-long benefits.Further experiments will show whether the approach is effective foryears or works in vein grafts. If gene therapy can eliminate orreduce existing plaques, as well as prevent their formation, itwould have even greater clinical usefulness. The researchers pointed out that efficient catheter-based or othertargeted delivery of gene therapy to the three main locations whereatherosclerosis is most harmful - the carotid, coronary, andfemoral (groin) arteries - might significantly reduce disabilityand mortality from atherosclerosis. "Localized one-time gene therapy might someday be an alternative oran important adjunct to systemic drugs such as statins thatpatients take for decades," Dichek said. "In gene-therapy trialsfor other diseases, one-time treatments have shown efficacy for atleast nine years and will likely continue to be effectiveindefinitely. Because atherosclerosis is a life-long threat, genetherapy that protects blood vessels for a lifetime makes a lot ofsense." Notes: This research study was supported by grants from the National HeartLung and Blood Institute of the National Institutes of Health, andthe John L. Locke, Jr. Charitable Trust. In addition to David Dichek, the study authors are Rowan Flynn, KunQian, Chongren Tang, Nagadhara Dronadula, Joshua M. Buckler, BoJiang, Shan Wen, all of the UW Department of Medicine, and Helen L.Dichek, of the UW Department of Pediatrics. The HDAd vector wasmade with materials supplied to the University of Washington byAdVec, Inc. The authors declared no conflict of interest. Source: Leila Gray University of Washington Additional References Citations. I am an expert from sinocoredrill.com, while we provides the quality product, such as Core Drill Rig Manufacturer , China Drill Rig Parts, Diamond Drilling Tools,and more.
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