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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...

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Autores principales: Marquez Loza, Laura I., Yuen, Eric C., McCray, Paul B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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