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Lentiviral Vectors for the Treatment and Prevention of Cystic Fibrosis Lung Disease
Despite the continued development of cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs for the treatment of cystic fibrosis (CF), the need for mutation agnostic treatments remains. In a sub-group of CF individuals with mutations that may not respond to modulators, such as th...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471883/ https://www.ncbi.nlm.nih.gov/pubmed/30875857 http://dx.doi.org/10.3390/genes10030218 |
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author | Marquez Loza, Laura I. Yuen, Eric C. McCray, Paul B. |
author_facet | Marquez Loza, Laura I. Yuen, Eric C. McCray, Paul B. |
author_sort | Marquez Loza, Laura I. |
collection | PubMed |
description | Despite the continued development of cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs for the treatment of cystic fibrosis (CF), the need for mutation agnostic treatments remains. In a sub-group of CF individuals with mutations that may not respond to modulators, such as those with nonsense mutations, CFTR gene transfer to airway epithelia offers the potential for an effective treatment. Lentiviral vectors are well-suited for this purpose because they transduce nondividing cells, and provide long-term transgene expression. Studies in primary cultures of human CF airway epithelia and CF animal models demonstrate the long-term correction of CF phenotypes and low immunogenicity using lentiviral vectors. Further development of CF gene therapy requires the investigation of optimal CFTR expression in the airways. Lentiviral vectors with improved safety features have minimized insertional mutagenesis safety concerns raised in early clinical trials for severe combined immunodeficiency using γ-retroviral vectors. Recent clinical trials using improved lentiviral vectors support the feasibility and safety of lentiviral gene therapy for monogenetic diseases. While work remains to be done before CF gene therapy reaches the bedside, recent advances in lentiviral vector development reviewed here are encouraging and suggest it could be tested in clinical studies in the near future. |
format | Online Article Text |
id | pubmed-6471883 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64718832019-04-27 Lentiviral Vectors for the Treatment and Prevention of Cystic Fibrosis Lung Disease Marquez Loza, Laura I. Yuen, Eric C. McCray, Paul B. Genes (Basel) Review Despite the continued development of cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs for the treatment of cystic fibrosis (CF), the need for mutation agnostic treatments remains. In a sub-group of CF individuals with mutations that may not respond to modulators, such as those with nonsense mutations, CFTR gene transfer to airway epithelia offers the potential for an effective treatment. Lentiviral vectors are well-suited for this purpose because they transduce nondividing cells, and provide long-term transgene expression. Studies in primary cultures of human CF airway epithelia and CF animal models demonstrate the long-term correction of CF phenotypes and low immunogenicity using lentiviral vectors. Further development of CF gene therapy requires the investigation of optimal CFTR expression in the airways. Lentiviral vectors with improved safety features have minimized insertional mutagenesis safety concerns raised in early clinical trials for severe combined immunodeficiency using γ-retroviral vectors. Recent clinical trials using improved lentiviral vectors support the feasibility and safety of lentiviral gene therapy for monogenetic diseases. While work remains to be done before CF gene therapy reaches the bedside, recent advances in lentiviral vector development reviewed here are encouraging and suggest it could be tested in clinical studies in the near future. MDPI 2019-03-14 /pmc/articles/PMC6471883/ /pubmed/30875857 http://dx.doi.org/10.3390/genes10030218 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Marquez Loza, Laura I. Yuen, Eric C. McCray, Paul B. Lentiviral Vectors for the Treatment and Prevention of Cystic Fibrosis Lung Disease |
title | Lentiviral Vectors for the Treatment and Prevention of Cystic Fibrosis Lung Disease |
title_full | Lentiviral Vectors for the Treatment and Prevention of Cystic Fibrosis Lung Disease |
title_fullStr | Lentiviral Vectors for the Treatment and Prevention of Cystic Fibrosis Lung Disease |
title_full_unstemmed | Lentiviral Vectors for the Treatment and Prevention of Cystic Fibrosis Lung Disease |
title_short | Lentiviral Vectors for the Treatment and Prevention of Cystic Fibrosis Lung Disease |
title_sort | lentiviral vectors for the treatment and prevention of cystic fibrosis lung disease |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471883/ https://www.ncbi.nlm.nih.gov/pubmed/30875857 http://dx.doi.org/10.3390/genes10030218 |
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