title: Comparison of DNA-lipid complexes and DNA alone for gene transfer to cystic fibrosis airway epithelia in vivo.
abstract: Cationic lipids show promise as vectors for transfer of CFTR cDNA to airway epithelia of patients with cystic fibrosis (CF). However, previous studies have not compared the effect of DNA-lipid to DNA alone. Recently, we developed a formulation of plasmid encoding CFTR (pCF1-CFTR) and cationic lipid (GL-67:DOPE) that generated greater gene transfer in mouse lung than previously described DNA-lipid vectors. Therefore, we tested the hypothesis that DNA-lipid complexes were more effective than DNA alone at transferring CFTR cDNA to airway epithelia in vivo. We administered complexes of DNA-lipid to one nostril and DNA alone to the other nostril in a randomized, double-blind study. Electrophysiologic measurements showed that DNA-lipid complexes partially corrected the Cl- transport defect. Importantly, the pCF1-CFTR plasmid alone was at least as effective as complexes of DNA with lipid. Measurements of vector-specific CFTR transcripts also showed gene transfer with both DNA-lipid and DNA alone. These results indicate that nonviral vectors can transfer CFTR cDNA to airway epithelia and at least partially restore the Cl- transport defect characteristic of CF. However, improvements in the overall efficacy of gene transfer are required to develop a treatment for CF.
authors.affiliation: Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zabner
authors.forename: S H
authors.initials: SH
authors.lastname: Cheng
authors.forename: D
authors.initials: D
authors.lastname: Meeker
authors.forename: J
authors.initials: J
authors.lastname: Launspach
authors.forename: R
authors.initials: R
authors.lastname: Balfour
authors.forename: M A
authors.initials: MA
authors.lastname: Perricone
authors.forename: J E
authors.initials: JE
authors.lastname: Morris
authors.forename: J
authors.initials: J
authors.lastname: Marshall
authors.forename: A
authors.initials: A
authors.lastname: Fasbender
authors.forename: A E
authors.initials: AE
authors.lastname: Smith
authors.forename: M J
authors.initials: MJ
authors.lastname: Welsh
mesh_terms: D000293:Adolescent; D000328:Adult; D000584:Amiloride / Q000494:pharmacology; D002713:Chlorine / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000378:metabolism / Q000628:therapy*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D004247:DNA / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005069:Evaluation Studies as Topic; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008055:Lipids / Q000276:immunology / Q000493:pharmacokinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D016133:Polymerase Chain Reaction; D013726:Terbutaline / Q000494:pharmacology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C505032:CFTR protein, human; D015850:Interleukin-6; D008055:Lipids; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D002713:Chlorine; D000584:Amiloride; D004247:DNA; D013726:Terbutaline