Gene therapy for cystic fibrosis: Challenges and prospects
Cystic fibrosis (CF) is a life-threatening autosomal-recessive disease caused by mutations in a single gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). CF effects multiple organs, and lung disease is the primary cause of mortality. The median age at death from CF is in the e...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.1015926/full |
| _version_ | 1817984435245547520 |
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| author | Hongshu Sui Xinghua Xu Yanping Su Zhaoqing Gong Minhua Yao Xiaocui Liu Ting Zhang Ziyao Jiang Tianhao Bai Junzuo Wang Jingjun Zhang Changlong Xu Changlong Xu Mingjiu Luo |
| author_facet | Hongshu Sui Xinghua Xu Yanping Su Zhaoqing Gong Minhua Yao Xiaocui Liu Ting Zhang Ziyao Jiang Tianhao Bai Junzuo Wang Jingjun Zhang Changlong Xu Changlong Xu Mingjiu Luo |
| author_sort | Hongshu Sui |
| collection | DOAJ |
| description | Cystic fibrosis (CF) is a life-threatening autosomal-recessive disease caused by mutations in a single gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). CF effects multiple organs, and lung disease is the primary cause of mortality. The median age at death from CF is in the early forties. CF was one of the first diseases to be considered for gene therapy, and efforts focused on treating CF lung disease began shortly after the CFTR gene was identified in 1989. However, despite the quickly established proof-of-concept for CFTR gene transfer in vitro and in clinical trials in 1990s, to date, 36 CF gene therapy clinical trials involving ∼600 patients with CF have yet to achieve their desired outcomes. The long journey to pursue gene therapy as a cure for CF encountered more difficulties than originally anticipated, but immense progress has been made in the past decade in the developments of next generation airway transduction viral vectors and CF animal models that reproduced human CF disease phenotypes. In this review, we look back at the history for the lessons learned from previous clinical trials and summarize the recent advances in the research for CF gene therapy, including the emerging CRISPR-based gene editing strategies. We also discuss the airway transduction vectors, large animal CF models, the complexity of CF pathogenesis and heterogeneity of CFTR expression in airway epithelium, which are the major challenges to the implementation of a successful CF gene therapy, and highlight the future opportunities and prospects. |
| first_indexed | 2024-04-13T23:45:26Z |
| format | Article |
| id | doaj.art-87be92cae9ba41919ea8add905177167 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T23:45:26Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-87be92cae9ba41919ea8add9051771672022-12-22T02:24:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.10159261015926Gene therapy for cystic fibrosis: Challenges and prospectsHongshu Sui0Xinghua Xu1Yanping Su2Zhaoqing Gong3Minhua Yao4Xiaocui Liu5Ting Zhang6Ziyao Jiang7Tianhao Bai8Junzuo Wang9Jingjun Zhang10Changlong Xu11Changlong Xu12Mingjiu Luo13Department of Histology and Embryology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Science, Jinan, Shandong, ChinaDepartment of Histology and Embryology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Science, Jinan, Shandong, ChinaDepartment of Histology and Embryology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Science, Jinan, Shandong, ChinaDepartment of Histology and Embryology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Science, Jinan, Shandong, ChinaDepartment of Histology and Embryology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Science, Jinan, Shandong, ChinaDepartment of Histology and Embryology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Science, Jinan, Shandong, ChinaDepartment of Histology and Embryology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Science, Jinan, Shandong, ChinaDepartment of Histology and Embryology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Science, Jinan, Shandong, ChinaShandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an, ChinaThe Affiliated Tai’an City Central Hospital of Qingdao University, Tai’an, Shandong, ChinaDepartment of Neurology, The Second Affiliated Hospital of Shandong First Medical University, Tai’an, Shandong, ChinaThe Reproductive Medical Center of Nanning Second People’s Hospital, Nanning, ChinaNational Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Bio-targeting Theranostics, Guangxi Medical University, Nanning, ChinaShandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an, ChinaCystic fibrosis (CF) is a life-threatening autosomal-recessive disease caused by mutations in a single gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). CF effects multiple organs, and lung disease is the primary cause of mortality. The median age at death from CF is in the early forties. CF was one of the first diseases to be considered for gene therapy, and efforts focused on treating CF lung disease began shortly after the CFTR gene was identified in 1989. However, despite the quickly established proof-of-concept for CFTR gene transfer in vitro and in clinical trials in 1990s, to date, 36 CF gene therapy clinical trials involving ∼600 patients with CF have yet to achieve their desired outcomes. The long journey to pursue gene therapy as a cure for CF encountered more difficulties than originally anticipated, but immense progress has been made in the past decade in the developments of next generation airway transduction viral vectors and CF animal models that reproduced human CF disease phenotypes. In this review, we look back at the history for the lessons learned from previous clinical trials and summarize the recent advances in the research for CF gene therapy, including the emerging CRISPR-based gene editing strategies. We also discuss the airway transduction vectors, large animal CF models, the complexity of CF pathogenesis and heterogeneity of CFTR expression in airway epithelium, which are the major challenges to the implementation of a successful CF gene therapy, and highlight the future opportunities and prospects.https://www.frontiersin.org/articles/10.3389/fphar.2022.1015926/fullcystic fibrosisgene therapyviral vectorsanimal modelsairway delivery |
| spellingShingle | Hongshu Sui Xinghua Xu Yanping Su Zhaoqing Gong Minhua Yao Xiaocui Liu Ting Zhang Ziyao Jiang Tianhao Bai Junzuo Wang Jingjun Zhang Changlong Xu Changlong Xu Mingjiu Luo Gene therapy for cystic fibrosis: Challenges and prospects Frontiers in Pharmacology cystic fibrosis gene therapy viral vectors animal models airway delivery |
| title | Gene therapy for cystic fibrosis: Challenges and prospects |
| title_full | Gene therapy for cystic fibrosis: Challenges and prospects |
| title_fullStr | Gene therapy for cystic fibrosis: Challenges and prospects |
| title_full_unstemmed | Gene therapy for cystic fibrosis: Challenges and prospects |
| title_short | Gene therapy for cystic fibrosis: Challenges and prospects |
| title_sort | gene therapy for cystic fibrosis challenges and prospects |
| topic | cystic fibrosis gene therapy viral vectors animal models airway delivery |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.1015926/full |
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