Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings
Adeno-associated viruses (AAVs) are the safest and most effective gene delivery vehicles to drive long-term transgene expression in gene therapy. While animal studies have shown promising results, the translatability of AAVs into clinical settings has been partly limited due to their restricted gene...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2021.809118/full |
| _version_ | 1818689563663532032 |
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| author | Hau Kiu Edna Au Mark Isalan Mark Isalan Michal Mielcarek Michal Mielcarek |
| author_facet | Hau Kiu Edna Au Mark Isalan Mark Isalan Michal Mielcarek Michal Mielcarek |
| author_sort | Hau Kiu Edna Au |
| collection | DOAJ |
| description | Adeno-associated viruses (AAVs) are the safest and most effective gene delivery vehicles to drive long-term transgene expression in gene therapy. While animal studies have shown promising results, the translatability of AAVs into clinical settings has been partly limited due to their restricted gene packaging capacities, off-target transduction, and immunogenicity. In this study, we analysed over two decades of AAV applications, in 136 clinical trials. This meta-analysis aims to provide an up-to-date overview of the use and successes of AAVs in clinical trials, while evaluating the approaches used to address the above challenges. First, this study reveals that the speed of novel AAV development has varied between therapeutic areas, with particular room for improvement in Central Nervous System disorders, where development has been slow. Second, the lack of dose-dependent toxicity and efficacy data indicates that optimal dosing regimes remain elusive. Third, more clinical data on the effectiveness of various immune-modulation strategies and gene editing approaches are required to direct future research and to accelerate the translation of AAV-mediated gene therapy into human applications. |
| first_indexed | 2024-12-17T12:12:06Z |
| format | Article |
| id | doaj.art-edfcdafbe7a74e8b9f415b2fef5f82ae |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-17T12:12:06Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-edfcdafbe7a74e8b9f415b2fef5f82ae2022-12-21T21:49:21ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-02-01810.3389/fmed.2021.809118809118Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical SettingsHau Kiu Edna Au0Mark Isalan1Mark Isalan2Michal Mielcarek3Michal Mielcarek4Department of Life Sciences, Imperial College London, London, United KingdomDepartment of Life Sciences, Imperial College London, London, United KingdomImperial College Centre for Synthetic Biology, Imperial College London, London, United KingdomDepartment of Life Sciences, Imperial College London, London, United KingdomImperial College Centre for Synthetic Biology, Imperial College London, London, United KingdomAdeno-associated viruses (AAVs) are the safest and most effective gene delivery vehicles to drive long-term transgene expression in gene therapy. While animal studies have shown promising results, the translatability of AAVs into clinical settings has been partly limited due to their restricted gene packaging capacities, off-target transduction, and immunogenicity. In this study, we analysed over two decades of AAV applications, in 136 clinical trials. This meta-analysis aims to provide an up-to-date overview of the use and successes of AAVs in clinical trials, while evaluating the approaches used to address the above challenges. First, this study reveals that the speed of novel AAV development has varied between therapeutic areas, with particular room for improvement in Central Nervous System disorders, where development has been slow. Second, the lack of dose-dependent toxicity and efficacy data indicates that optimal dosing regimes remain elusive. Third, more clinical data on the effectiveness of various immune-modulation strategies and gene editing approaches are required to direct future research and to accelerate the translation of AAV-mediated gene therapy into human applications.https://www.frontiersin.org/articles/10.3389/fmed.2021.809118/fulladeno-associated virusgene therapytropismclinical trialspromoters |
| spellingShingle | Hau Kiu Edna Au Mark Isalan Mark Isalan Michal Mielcarek Michal Mielcarek Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings Frontiers in Medicine adeno-associated virus gene therapy tropism clinical trials promoters |
| title | Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings |
| title_full | Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings |
| title_fullStr | Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings |
| title_full_unstemmed | Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings |
| title_short | Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings |
| title_sort | gene therapy advances a meta analysis of aav usage in clinical settings |
| topic | adeno-associated virus gene therapy tropism clinical trials promoters |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2021.809118/full |
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