nebulisation of receptor-targeted nanocomplexes for gene delivery to the airway epithelium的nebulisation receptor-targeted nanocomplexes气道上皮基因传递.pdfVIP

Nebulisation of Receptor-Targeted Nanocomplexes for Gene Delivery to the Airway Epithelium 1 2 1 2 Maria D. I. Manunta , Robin J. McAnulty , Aristides D. Tagalakis , Stephen E. Bottoms , Frederick 3 3 3 2 4 Campbell , Helen C. Hailes , Alethea B. Tabor , Geoffrey J. Laurent , Christopher O’Callaghan , Stephen L. Hart1* 1 Wolfson Centre for Gene Therapy of Childhood Disease, UCL Institute of Child Health, University College London, London, United Kingdom, 2 Centre for Respiratory Research, University College London, London, United Kingdom, 3 Department of Chemistry, University College London, London, United Kingdom, 4 Department of Infection, Immunity and Inflammation, University of Leicester, Leicester Royal Infirmary, Leicester, United Kingdom Abstract Background: Gene therapy mediated by synthetic vectors may provide opportunities for new treatments for cystic fibrosis (CF) via aerosolisation. Vectors for CF must transfect the airway epithelium efficiently and not cause inflammation so they are suitable for repeated dosing. The inhaled aerosol should be deposited in the airways since the cystic fibrosis transmembrane conductance regulator gene (CFTR) is expressed predominantly in the epithelium of the submucosal glands and in the surface airway epithelium. The aim of this project was to develop an optimised aerosol delivery approach applicable to treatment of CF lung disease by gene therapy. Methodology: The vector suspension investigated in this study comprises receptor-targeting peptides, cationic liposomes and plasmid DNA that self-assemble by el