{"id":2763,"date":"2017-06-29T21:05:00","date_gmt":"2017-06-30T01:05:00","guid":{"rendered":"https:\/\/www.med.unc.edu\/genetics\/newly-designed-viral-vectors-could-lead-to-improved-gene-therapies\/"},"modified":"2018-02-06T17:08:20","modified_gmt":"2018-02-06T22:08:20","slug":"newly-designed-viral-vectors-could-lead-to-improved-gene-therapies","status":"publish","type":"post","link":"https:\/\/www.med.unc.edu\/genetics\/newly-designed-viral-vectors-could-lead-to-improved-gene-therapies\/","title":{"rendered":"Newly designed viral vectors could lead to improved gene therapies"},"content":{"rendered":"

<\/p>\n

UNC and University of Florida researchers created viruses to deliver gene therapies while evading pre-existing immune system responses. Aravind Asokan, PhD, led the research team at UNC.<\/p>\n

\n
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Aravind Asokan, PhD<\/figcaption><\/figure>\n<\/div>\n

June 15, 2017<\/p>\n

CHAPEL HILL, NC \u2013 For many patients, participating in gene therapy clinical trials isn\u2019t an option because their immune system recognizes and fights the helpful virus used for treatment. Now, University of Florida Health and University of North Carolina researchers have found a solution that may allow viruses used for gene therapy to evade the body\u2019s normal immune response.<\/p>\n

The discovery, published in the Proceedings of the National Academy of Sciences<\/i>, is a crucial step in averting the immune response that prevents many people from taking part in clinical trials for various disorders, according to co-author Mavis Agbandje-McKenna, PhD, a professor in the University of Florida College of Medicine department of biochemistry and molecular biology and director of the Center for Structural Biology.<\/p>\n

During gene therapy, engineered viruses are used to deliver new genes to a patient\u2019s cells. While the recombinant adeno-associated virus, or AAV, is effective at delivering its genetic cargo, prior natural exposure to AAV results in antibodies in some people. As many as 70 percent of patients have pre-existing immunity that makes them ineligible for gene therapy clinical trials, Agbandje-McKenna said.<\/p>\n

\u201cThe findings provide a road map for designing virus strains that can evade neutralizing antibodies,\u201d said Aravind Asokan, PhD, an associate professor in the department of genetics at the University of North Carolina School of Medicine, who led the study.<\/p>\n

University of Florida first identified the structural \u201cfootprints\u201d where pre-existing antibodies interact with the virus, using an cryo-electron microscope. The UNC researchers then evolved new viral protein shells. Using serum from mice, rhesus monkeys, and humans, the researchers showed that the redesigned virus can slip past the immune system.<\/p>\n

\u201cThis is the blueprint for producing AAV strains that could help more patients become eligible for human gene therapy. Now we know how to do it,\u201d Agbandje-McKenna said.<\/p>\n

While the findings prove that one variation of AAV can be evolved, further study in preclinical models is needed before the approach can be tested in humans. Next, the immune profile of one particularly promising virus variant will need to be evaluated in a larger number of human serum samples, and dose-finding studies are needed in certain animal models. Researchers may also need to study whether the same virus-manipulating technique can be used in a broader range of gene therapy viruses, Agbandje-McKenna said.<\/p>\n

Although human gene therapy remains an emerging field and has yet to reach patients on a wide scale, researchers elsewhere have used AAV therapy to successfully treat hemophilia, a blood-clotting disorder, in a small trial. It has also been or is now being studied as a way to treat hereditary blindness, certain immune deficiencies, neurological and metabolic disorders, and certain cancers.<\/p>\n

The latest findings are the result of more than 10 years of studying the interactions between viruses and antibodies and a long-standing collaboration with Asokan, who heads the synthetic virology group at the UNC Gene Therapy Center.<\/p>\n

Grants from the National Institutes of Health supported the research.<\/i><\/p>\n

This story by Mark Derewicz<\/a> and Rossana Passaniti<\/a> is originally published on the UNC School of Medicine Newsroom<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"

UNC and University of Florida researchers created viruses to deliver gene therapies while evading pre-existing immune system responses. Aravind Asokan, PhD, led the research team at UNC. June 15, 2017 CHAPEL HILL, NC \u2013 For many patients, participating in gene therapy clinical trials isn\u2019t an option because their immune system recognizes and fights the helpful … Read more<\/a><\/p>\n","protected":false},"author":22429,"featured_media":2764,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[2],"tags":[],"class_list":["post-2763","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","odd"],"acf":[],"yoast_head":"\nNewly designed viral vectors could lead to improved gene therapies | Department of Genetics<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.med.unc.edu\/genetics\/newly-designed-viral-vectors-could-lead-to-improved-gene-therapies\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Newly designed viral vectors could lead to improved gene therapies | Department of Genetics\" \/>\n<meta property=\"og:description\" content=\"UNC and University of Florida researchers created viruses to deliver gene therapies while evading pre-existing immune system responses. 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