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Type: Journal article
Title: Recovery of airway cystic fibrosis transmembrane conductance regulator function in mice with cystic fibrosis after single-dose lentivirus-mediated gene transfer
Author: Limberis, M.
Anson, D.
Fuller, M.
Parsons, D.
Citation: Human Gene Therapy, 2002; 13(16):1961-1970
Publisher: Mary Ann Liebert Inc Publ
Issue Date: 2002
ISSN: 1043-0342
Abstract: The potential for gene therapy to be an effective treatment for cystic fibrosis (CF) airway disease has been limited by inefficient gene transfer vector particle delivery and lack of persistent gene expression. We have developed an airway conditioning process that, when combined with a human immunodeficiency virus (HIV)-derived lentivirus (LV) vector, resulted in persistent in vivo expression of transgenes in airway epithelium. Pretreatment of mouse nasal epithelium with the detergent lysophosphatidylcholine (LPC) prior to instillation of a single dose of an LV vector carrying the LacZ marker gene produced significant LacZ gene expression in nasal airway epithelium for at least 92 days. Transduction of the cystic fibrosis transmembrane conductance regulator (CFTR) gene using the same LV vector system resulted in partial recovery of electrophysiologic function in the nasal airway epithelium of CF mice (cftr(tm1Unc) knockout) for at least 110 days. This first demonstration of LV-mediated in vivo recovery of CFTR function in CF airway epithelium illustrates the potential of combining a preconditioning of the airway surface with a simple and brief LV vector exposure to produce therapeutic gene expression in airway.
Keywords: Nasal Mucosa; 3T3 Cells; Animals; Mice, Transgenic; Humans; Mice; Lentivirus; Lysophosphatidylcholines; Cystic Fibrosis Transmembrane Conductance Regulator; Membrane Glycoproteins; Viral Envelope Proteins; Gene Transfer Techniques; HIV Long Terminal Repeat; Heterozygote; Lac Operon; Genetic Vectors; Time Factors
RMID: 0020021117
DOI: 10.1089/10430340260355365
Appears in Collections:Paediatrics publications

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