title: Progress with Recombinant Adeno-Associated Virus Vectors for Gene Therapy of Alpha-1 Antitrypsin Deficiency.
abstract: The pathway to a clinical gene therapy product often involves many changes of course and strategy before obtaining successful results. Here we outline the methodologies, both clinical and preclinical, that went into developing a gene therapy approach to the treatment of alpha-1 antitrypsin deficiency lung disease using muscle-targeted recombinant adeno-associated virus. From initial gene construct development in mouse models through multiple rounds of safety and biodistribution studies in rodents, rabbits, and nonhuman primates to ultimate human trials, this review seeks to provide insight into what clinical translation entails and could thereby inform the process for future investigators.
authors.affiliation: 1 Gene Therapy Center, University of Massachusetts Medical School , Worcester, MA 01655.
authors.forename: Alisha M
authors.initials: AM
authors.lastname: Gruntman
authors.affiliation: 1 Gene Therapy Center, University of Massachusetts Medical School , Worcester, MA 01655.|2 Department of Pediatrics, University of Massachusetts Medical School , Worcester, MA 01655.|3 Microbiology & Physiologic Systems, University of Massachusetts Medical School , Worcester, MA 01655.
authors.forename: Terence R
authors.initials: TR
authors.lastname: Flotte
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics; D006801:Humans; D019896:alpha 1-Antitrypsin Deficiency / Q000628:therapy*