title: Modulation of Treg function improves adenovirus vector-mediated gene expression in the airway.
abstract: Virus vector-mediated gene transfer has been developed as a treatment for cystic fibrosis (CF) airway disease, a lethal inherited disorder caused by somatic mutations in the cystic fibrosis transmembrane conductance regulator gene. The pathological proinflammatory environment of CF as well as the naïve and adaptive immunity induced by the virus vector itself limits the effectiveness of gene therapy for CF airway. Here, we report the use of an HDAC inhibitor, valproic acid (VPA), to enhance the activity of the regulatory T cells (T(reg)) and to improve the expression of virus vector-mediated gene transfer to the respiratory epithelium. Our study demonstrates the potential utility of VPA, a drug used for over 50 years in humans as an anticonvulsant and mood-stabilizer, in controlling inflammation and improving the efficacy of gene transfer in CF airway.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Nagai
authors.affiliation: 1] Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA [2] Gene Therapy Program, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Limberis
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D003550:Cystic Fibrosis / Q000276:immunology* / Q000473:pathology; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018181:Mice, Inbred CFTR / Q000235:genetics* / Q000276:immunology; D011014:Pneumonia / Q000276:immunology* / Q000628:therapy; D020545:Respiratory Mucosa / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D014635:Valproic Acid