Adeno-associated virus as a delivery vector for gene therapy of human diseases
Abstract Adeno-associated virus (AAV) has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different tissues. Recombinant AAV (rAAV) has been engineered for enhanced specificity and developed as a too...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-04-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-024-01780-w |
| _version_ | 1827291298363604992 |
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| author | Jiang-Hui Wang Dominic J. Gessler Wei Zhan Thomas L. Gallagher Guangping Gao |
| author_facet | Jiang-Hui Wang Dominic J. Gessler Wei Zhan Thomas L. Gallagher Guangping Gao |
| author_sort | Jiang-Hui Wang |
| collection | DOAJ |
| description | Abstract Adeno-associated virus (AAV) has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different tissues. Recombinant AAV (rAAV) has been engineered for enhanced specificity and developed as a tool for treating various diseases. However, as rAAV is being more widely used as a therapy, the increased demand has created challenges for the existing manufacturing methods. Seven rAAV-based gene therapy products have received regulatory approval, but there continue to be concerns about safely using high-dose viral therapies in humans, including immune responses and adverse effects such as genotoxicity, hepatotoxicity, thrombotic microangiopathy, and neurotoxicity. In this review, we explore AAV biology with an emphasis on current vector engineering strategies and manufacturing technologies. We discuss how rAAVs are being employed in ongoing clinical trials for ocular, neurological, metabolic, hematological, neuromuscular, and cardiovascular diseases as well as cancers. We outline immune responses triggered by rAAV, address associated side effects, and discuss strategies to mitigate these reactions. We hope that discussing recent advancements and current challenges in the field will be a helpful guide for researchers and clinicians navigating the ever-evolving landscape of rAAV-based gene therapy. |
| first_indexed | 2024-04-24T12:34:41Z |
| format | Article |
| id | doaj.art-0d352d9c4b0c45b6a1cdc849a6677099 |
| institution | Directory Open Access Journal |
| issn | 2059-3635 |
| language | English |
| last_indexed | 2024-04-24T12:34:41Z |
| publishDate | 2024-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj.art-0d352d9c4b0c45b6a1cdc849a66770992024-04-07T11:32:21ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352024-04-019113310.1038/s41392-024-01780-wAdeno-associated virus as a delivery vector for gene therapy of human diseasesJiang-Hui Wang0Dominic J. Gessler1Wei Zhan2Thomas L. Gallagher3Guangping Gao4Horae Gene Therapy Center, University of Massachusetts Chan Medical SchoolHorae Gene Therapy Center, University of Massachusetts Chan Medical SchoolHorae Gene Therapy Center, University of Massachusetts Chan Medical SchoolHorae Gene Therapy Center, University of Massachusetts Chan Medical SchoolHorae Gene Therapy Center, University of Massachusetts Chan Medical SchoolAbstract Adeno-associated virus (AAV) has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different tissues. Recombinant AAV (rAAV) has been engineered for enhanced specificity and developed as a tool for treating various diseases. However, as rAAV is being more widely used as a therapy, the increased demand has created challenges for the existing manufacturing methods. Seven rAAV-based gene therapy products have received regulatory approval, but there continue to be concerns about safely using high-dose viral therapies in humans, including immune responses and adverse effects such as genotoxicity, hepatotoxicity, thrombotic microangiopathy, and neurotoxicity. In this review, we explore AAV biology with an emphasis on current vector engineering strategies and manufacturing technologies. We discuss how rAAVs are being employed in ongoing clinical trials for ocular, neurological, metabolic, hematological, neuromuscular, and cardiovascular diseases as well as cancers. We outline immune responses triggered by rAAV, address associated side effects, and discuss strategies to mitigate these reactions. We hope that discussing recent advancements and current challenges in the field will be a helpful guide for researchers and clinicians navigating the ever-evolving landscape of rAAV-based gene therapy.https://doi.org/10.1038/s41392-024-01780-w |
| spellingShingle | Jiang-Hui Wang Dominic J. Gessler Wei Zhan Thomas L. Gallagher Guangping Gao Adeno-associated virus as a delivery vector for gene therapy of human diseases Signal Transduction and Targeted Therapy |
| title | Adeno-associated virus as a delivery vector for gene therapy of human diseases |
| title_full | Adeno-associated virus as a delivery vector for gene therapy of human diseases |
| title_fullStr | Adeno-associated virus as a delivery vector for gene therapy of human diseases |
| title_full_unstemmed | Adeno-associated virus as a delivery vector for gene therapy of human diseases |
| title_short | Adeno-associated virus as a delivery vector for gene therapy of human diseases |
| title_sort | adeno associated virus as a delivery vector for gene therapy of human diseases |
| url | https://doi.org/10.1038/s41392-024-01780-w |
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