Birth of a new therapeutic platform: 47 years of adeno-associated virus biology from virus discovery to licensed gene therapy
Gene Therapy Center; Department of Pediatrics
Medical Subject Headings
Clinical Trials as Topic; Dependovirus; Evolution, Molecular; Genetic Therapy; *Genetic Vectors; History, 20th Century; History, 21st Century; Humans; National Institutes of Health (U.S.); Phylogeny; United States
Genetic Processes | History of Science, Technology, and Medicine | Molecular Genetics | Therapeutics | Virology
Within American biomedical research, as supported primarily by the National Institutes of Health (NIH) since the post–World War II era, it has been considered axiomatic that investments in discovery research will ultimately lead to the development of novel approaches to diagnostics and therapeutics that will improve the health and well-being of citizens of the United States and the broader world. I reflect here in a historical context on how one such series of investments in discovery has resulted in the emergence of the first licensed human gene therapy product in Europe, namely Glybera. Glybera (alipogene tiparvovec) is a recombinant adeno-associated virus (rAAV) vector with AAV2 inverted terminal repeats (ITRs) encapsidated into AAV1 capsids (so-called rAAV2/1, or, for this purpose, rAAV1), which, when administered intramuscularly, can result in expression of sufficient levels of lipoprotein lipase (LPL) to be considered a safe and effective treatment of LPL deficiency. It was licensed in the European Union in November 2012, 47 years after the near simultaneous discovery of AAV in laboratories at the NIH Bethesda campus and at the University of Pittsburgh. I trace key milestones in the progress from the discovery of the virus, to its use as a platform for an approved therapeutic product.
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Citation: Mol Ther. 2013 Nov;21(11):1976-81. doi: 10.1038/mt.2013.226. Link to article on publisher's site
Flotte, Terence R., "Birth of a new therapeutic platform: 47 years of adeno-associated virus biology from virus discovery to licensed gene therapy" (2013). University of Massachusetts Medical School Faculty Publications. 821.