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Transcriptome Profiling and Molecular Therapeutic Advances in Cystic Fibrosis: Recent Insights

In cystic fibrosis (CF), mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene disrupt the capacity of the encoded protein to function as a channel to transport chloride ions and water across cell membranes. The consequences are deleterious, system-wide, and immensely vari...

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Autores principales: Ideozu, Justin E., Zhang, Xi, McColley, Susanna, Levy, Hara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470978/
https://www.ncbi.nlm.nih.gov/pubmed/30813620
http://dx.doi.org/10.3390/genes10030180
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author Ideozu, Justin E.
Zhang, Xi
McColley, Susanna
Levy, Hara
author_facet Ideozu, Justin E.
Zhang, Xi
McColley, Susanna
Levy, Hara
author_sort Ideozu, Justin E.
collection PubMed
description In cystic fibrosis (CF), mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene disrupt the capacity of the encoded protein to function as a channel to transport chloride ions and water across cell membranes. The consequences are deleterious, system-wide, and immensely variable, even among patients with the same CFTR genotype. This underscores the need to characterize the mechanisms contributing to CF pathophysiology. Gene replacement and gene editing therapies have been pursued intensively and are expected to provide a one-time treatment for CF. However, gene replacement therapy is limited by the lack of efficient vectors to deliver functional copies of CFTR to cells without immunological complications, while gene editing technologies such as CRISPR/Cas9 are still in their infancy, mainly useful in somatic cells and limited by off-target insertions. Small molecule treatments targeted at potentiating or correcting CFTR have shown clinical benefits, but they are limited to a few CFTR mutations and insufficient to overcome challenges related to clinical heterogeneity. Transcriptome profiling approaches have emerged as robust tools capable of characterizing phenotypic variability and revealing novel molecular targets with therapeutic potential for CF. We summarize current insights gained through transcriptome profiling approaches in CF studies and recent advances in molecular therapeutics.
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spelling pubmed-64709782019-04-27 Transcriptome Profiling and Molecular Therapeutic Advances in Cystic Fibrosis: Recent Insights Ideozu, Justin E. Zhang, Xi McColley, Susanna Levy, Hara Genes (Basel) Review In cystic fibrosis (CF), mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene disrupt the capacity of the encoded protein to function as a channel to transport chloride ions and water across cell membranes. The consequences are deleterious, system-wide, and immensely variable, even among patients with the same CFTR genotype. This underscores the need to characterize the mechanisms contributing to CF pathophysiology. Gene replacement and gene editing therapies have been pursued intensively and are expected to provide a one-time treatment for CF. However, gene replacement therapy is limited by the lack of efficient vectors to deliver functional copies of CFTR to cells without immunological complications, while gene editing technologies such as CRISPR/Cas9 are still in their infancy, mainly useful in somatic cells and limited by off-target insertions. Small molecule treatments targeted at potentiating or correcting CFTR have shown clinical benefits, but they are limited to a few CFTR mutations and insufficient to overcome challenges related to clinical heterogeneity. Transcriptome profiling approaches have emerged as robust tools capable of characterizing phenotypic variability and revealing novel molecular targets with therapeutic potential for CF. We summarize current insights gained through transcriptome profiling approaches in CF studies and recent advances in molecular therapeutics. MDPI 2019-02-26 /pmc/articles/PMC6470978/ /pubmed/30813620 http://dx.doi.org/10.3390/genes10030180 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
Ideozu, Justin E.
Zhang, Xi
McColley, Susanna
Levy, Hara
Transcriptome Profiling and Molecular Therapeutic Advances in Cystic Fibrosis: Recent Insights
title Transcriptome Profiling and Molecular Therapeutic Advances in Cystic Fibrosis: Recent Insights
title_full Transcriptome Profiling and Molecular Therapeutic Advances in Cystic Fibrosis: Recent Insights
title_fullStr Transcriptome Profiling and Molecular Therapeutic Advances in Cystic Fibrosis: Recent Insights
title_full_unstemmed Transcriptome Profiling and Molecular Therapeutic Advances in Cystic Fibrosis: Recent Insights
title_short Transcriptome Profiling and Molecular Therapeutic Advances in Cystic Fibrosis: Recent Insights
title_sort transcriptome profiling and molecular therapeutic advances in cystic fibrosis: recent insights
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470978/
https://www.ncbi.nlm.nih.gov/pubmed/30813620
http://dx.doi.org/10.3390/genes10030180
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