Potential of helper-dependent Adenoviral vectors in CRISPR-cas9-mediated lung gene therapy
Abstract Since CRISPR/Cas9 was harnessed to edit DNA, the field of gene therapy has witnessed great advances in gene editing. New avenues were created for the treatment of diseases such as Cystic Fibrosis (CF). CF is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFT...
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| Format: | Article |
| Language: | English |
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BMC
2021-07-01
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| Series: | Cell & Bioscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13578-021-00662-w |
| _version_ | 1819134606476050432 |
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| author | Ranmal Avinash Bandara Ziyan Rachel Chen Jim Hu |
| author_facet | Ranmal Avinash Bandara Ziyan Rachel Chen Jim Hu |
| author_sort | Ranmal Avinash Bandara |
| collection | DOAJ |
| description | Abstract Since CRISPR/Cas9 was harnessed to edit DNA, the field of gene therapy has witnessed great advances in gene editing. New avenues were created for the treatment of diseases such as Cystic Fibrosis (CF). CF is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Despite the success of gene editing with the CRISPR/Cas9 in vitro, challenges still exist when using CRISPR/Cas9 in vivo to cure CF lung disease. The delivery of CRISPR/Cas9 into lungs, as well as the difficulty to achieve the efficiency required for clinical efficacy, has brought forth new challenges. Viral and non-viral vectors have been shown to deliver DNA successfully in vivo, but the sustained expression of CFTR was not adequate. Before the introduction of Helper-Dependent Adenoviral vectors (HD-Ad), clinical trials of treating pulmonary genetic diseases with first-generation viral vectors have shown limited efficacy. With the advantages of larger capacity and lower immunogenicity of HD-Ad, together with the versatility of the CRISPR/Cas9 system, delivering CRISPR/Cas9 to the airway with HD-Ad for lung gene therapy shows great potential. In this review, we discuss the status of the application of CRISPR/Cas9 in CF gene therapy, the existing challenges in the field, as well as new hurdles introduced by the presence of CRISPR/Cas9 in the lungs. Through the analysis of these challenges, we present the potential of CRISPR/Cas9-mediated lung gene therapy using HD-Ad vectors with Cystic Fibrosis lung disease as a model of therapy. |
| first_indexed | 2024-12-22T10:05:52Z |
| format | Article |
| id | doaj.art-133033e0334b44f0b776f8c43e51844f |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-12-22T10:05:52Z |
| publishDate | 2021-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-133033e0334b44f0b776f8c43e51844f2022-12-21T18:29:58ZengBMCCell & Bioscience2045-37012021-07-011111910.1186/s13578-021-00662-wPotential of helper-dependent Adenoviral vectors in CRISPR-cas9-mediated lung gene therapyRanmal Avinash Bandara0Ziyan Rachel Chen1Jim Hu2Programmes in Translational Medicine, Research Institute, Hospital for Sick ChildrenProgrammes in Translational Medicine, Research Institute, Hospital for Sick ChildrenProgrammes in Translational Medicine, Research Institute, Hospital for Sick ChildrenAbstract Since CRISPR/Cas9 was harnessed to edit DNA, the field of gene therapy has witnessed great advances in gene editing. New avenues were created for the treatment of diseases such as Cystic Fibrosis (CF). CF is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Despite the success of gene editing with the CRISPR/Cas9 in vitro, challenges still exist when using CRISPR/Cas9 in vivo to cure CF lung disease. The delivery of CRISPR/Cas9 into lungs, as well as the difficulty to achieve the efficiency required for clinical efficacy, has brought forth new challenges. Viral and non-viral vectors have been shown to deliver DNA successfully in vivo, but the sustained expression of CFTR was not adequate. Before the introduction of Helper-Dependent Adenoviral vectors (HD-Ad), clinical trials of treating pulmonary genetic diseases with first-generation viral vectors have shown limited efficacy. With the advantages of larger capacity and lower immunogenicity of HD-Ad, together with the versatility of the CRISPR/Cas9 system, delivering CRISPR/Cas9 to the airway with HD-Ad for lung gene therapy shows great potential. In this review, we discuss the status of the application of CRISPR/Cas9 in CF gene therapy, the existing challenges in the field, as well as new hurdles introduced by the presence of CRISPR/Cas9 in the lungs. Through the analysis of these challenges, we present the potential of CRISPR/Cas9-mediated lung gene therapy using HD-Ad vectors with Cystic Fibrosis lung disease as a model of therapy.https://doi.org/10.1186/s13578-021-00662-wAdenovirusGene therapyAirway gene deliveryCas9Cystic fibrosis |
| spellingShingle | Ranmal Avinash Bandara Ziyan Rachel Chen Jim Hu Potential of helper-dependent Adenoviral vectors in CRISPR-cas9-mediated lung gene therapy Cell & Bioscience Adenovirus Gene therapy Airway gene delivery Cas9 Cystic fibrosis |
| title | Potential of helper-dependent Adenoviral vectors in CRISPR-cas9-mediated lung gene therapy |
| title_full | Potential of helper-dependent Adenoviral vectors in CRISPR-cas9-mediated lung gene therapy |
| title_fullStr | Potential of helper-dependent Adenoviral vectors in CRISPR-cas9-mediated lung gene therapy |
| title_full_unstemmed | Potential of helper-dependent Adenoviral vectors in CRISPR-cas9-mediated lung gene therapy |
| title_short | Potential of helper-dependent Adenoviral vectors in CRISPR-cas9-mediated lung gene therapy |
| title_sort | potential of helper dependent adenoviral vectors in crispr cas9 mediated lung gene therapy |
| topic | Adenovirus Gene therapy Airway gene delivery Cas9 Cystic fibrosis |
| url | https://doi.org/10.1186/s13578-021-00662-w |
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