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Gene therapy for the treatment of cystic fibrosis

Gene therapy is being developed as a novel treatment for cystic fibrosis (CF), a condition that has hitherto been widely-researched yet for which no treatment exists that halts the progression of lung disease. Gene therapy involves the transfer of correct copies of cystic fibrosis transmembrane cond...

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Autores principales: Burney, Tabinda J, Davies, Jane C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681190/
https://www.ncbi.nlm.nih.gov/pubmed/23776378
http://dx.doi.org/10.2147/TACG.S8873
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author Burney, Tabinda J
Davies, Jane C
author_facet Burney, Tabinda J
Davies, Jane C
author_sort Burney, Tabinda J
collection PubMed
description Gene therapy is being developed as a novel treatment for cystic fibrosis (CF), a condition that has hitherto been widely-researched yet for which no treatment exists that halts the progression of lung disease. Gene therapy involves the transfer of correct copies of cystic fibrosis transmembrane conductance regulator (CFTR) DNA to the epithelial cells in the airways. The cloning of the CFTR gene in 1989 led to proof-of-principle studies of CFTR gene transfer in vitro and in animal models. The earliest clinical trials in CF patients were conducted in 1993 and used viral and non-viral gene transfer agents in both the nasal and bronchial airway epithelium. To date, studies have focused largely on molecular or bioelectric (chloride secretion) outcome measures, many demonstrating evidence of CFTR expression, but few have attempted to achieve clinical efficacy. As CF is a lifelong disease, turnover of the airway epithelium necessitates repeat administration. To date, this has been difficult to achieve with viral gene transfer agents due to host recognition leading to loss of expression. The UK Cystic Fibrosis Gene Therapy Consortium (Imperial College London, University of Edinburgh and University of Oxford) is currently working on a large and ambitious program to establish the clinical benefits of CF gene therapy. Wave 1, which has reached the clinic, uses a non-viral vector. A single-dose safety trial is nearing completion and a multi-dose clinical trial is shortly due to start; this will be powered for clinically-relevant changes. Wave 2, more futuristically, will look at the potential of lentiviruses, which have long-lasting expression. This review will summarize the current status of translational research in CF gene therapy.
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spelling pubmed-36811902013-06-17 Gene therapy for the treatment of cystic fibrosis Burney, Tabinda J Davies, Jane C Appl Clin Genet Review Gene therapy is being developed as a novel treatment for cystic fibrosis (CF), a condition that has hitherto been widely-researched yet for which no treatment exists that halts the progression of lung disease. Gene therapy involves the transfer of correct copies of cystic fibrosis transmembrane conductance regulator (CFTR) DNA to the epithelial cells in the airways. The cloning of the CFTR gene in 1989 led to proof-of-principle studies of CFTR gene transfer in vitro and in animal models. The earliest clinical trials in CF patients were conducted in 1993 and used viral and non-viral gene transfer agents in both the nasal and bronchial airway epithelium. To date, studies have focused largely on molecular or bioelectric (chloride secretion) outcome measures, many demonstrating evidence of CFTR expression, but few have attempted to achieve clinical efficacy. As CF is a lifelong disease, turnover of the airway epithelium necessitates repeat administration. To date, this has been difficult to achieve with viral gene transfer agents due to host recognition leading to loss of expression. The UK Cystic Fibrosis Gene Therapy Consortium (Imperial College London, University of Edinburgh and University of Oxford) is currently working on a large and ambitious program to establish the clinical benefits of CF gene therapy. Wave 1, which has reached the clinic, uses a non-viral vector. A single-dose safety trial is nearing completion and a multi-dose clinical trial is shortly due to start; this will be powered for clinically-relevant changes. Wave 2, more futuristically, will look at the potential of lentiviruses, which have long-lasting expression. This review will summarize the current status of translational research in CF gene therapy. Dove Medical Press 2012-05-29 /pmc/articles/PMC3681190/ /pubmed/23776378 http://dx.doi.org/10.2147/TACG.S8873 Text en © 2012 Burney and Davies, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Review
Burney, Tabinda J
Davies, Jane C
Gene therapy for the treatment of cystic fibrosis
title Gene therapy for the treatment of cystic fibrosis
title_full Gene therapy for the treatment of cystic fibrosis
title_fullStr Gene therapy for the treatment of cystic fibrosis
title_full_unstemmed Gene therapy for the treatment of cystic fibrosis
title_short Gene therapy for the treatment of cystic fibrosis
title_sort gene therapy for the treatment of cystic fibrosis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681190/
https://www.ncbi.nlm.nih.gov/pubmed/23776378
http://dx.doi.org/10.2147/TACG.S8873
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