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Immunogenicity and toxicity of AAV gene therapy
Gene transfer using adeno-associated viral (AAV) vectors has made tremendous progress in the last decade and has achieved cures of debilitating diseases such as hemophilia A and B. Nevertheless, progress is still being hampered by immune responses against the AAV capsid antigens or the transgene pro...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9411526/ https://www.ncbi.nlm.nih.gov/pubmed/36032092 http://dx.doi.org/10.3389/fimmu.2022.975803 |
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author | Ertl, Hildegund C. J. |
author_facet | Ertl, Hildegund C. J. |
author_sort | Ertl, Hildegund C. J. |
collection | PubMed |
description | Gene transfer using adeno-associated viral (AAV) vectors has made tremendous progress in the last decade and has achieved cures of debilitating diseases such as hemophilia A and B. Nevertheless, progress is still being hampered by immune responses against the AAV capsid antigens or the transgene products. Immunosuppression designed to blunt T cell responses has shown success in some patients but failed in others especially if they received very high AAV vectors doses. Although it was initially thought that AAV vectors induce only marginal innate responses below the threshold of systemic symptoms recent trials have shown that complement activation can results in serious adverse events. Dorsal root ganglia toxicity has also been identified as a complication of high vector doses as has severe hepatotoxicity. Most of the critical complications occur in patients who are treated with very high vector doses indicating that the use of more efficient AAV vectors to allow for dose sparing or giving smaller doses repeatedly, the latter in conjunction with antibody or B cell depleting measures, should be explored. |
format | Online Article Text |
id | pubmed-9411526 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94115262022-08-27 Immunogenicity and toxicity of AAV gene therapy Ertl, Hildegund C. J. Front Immunol Immunology Gene transfer using adeno-associated viral (AAV) vectors has made tremendous progress in the last decade and has achieved cures of debilitating diseases such as hemophilia A and B. Nevertheless, progress is still being hampered by immune responses against the AAV capsid antigens or the transgene products. Immunosuppression designed to blunt T cell responses has shown success in some patients but failed in others especially if they received very high AAV vectors doses. Although it was initially thought that AAV vectors induce only marginal innate responses below the threshold of systemic symptoms recent trials have shown that complement activation can results in serious adverse events. Dorsal root ganglia toxicity has also been identified as a complication of high vector doses as has severe hepatotoxicity. Most of the critical complications occur in patients who are treated with very high vector doses indicating that the use of more efficient AAV vectors to allow for dose sparing or giving smaller doses repeatedly, the latter in conjunction with antibody or B cell depleting measures, should be explored. Frontiers Media S.A. 2022-08-12 /pmc/articles/PMC9411526/ /pubmed/36032092 http://dx.doi.org/10.3389/fimmu.2022.975803 Text en Copyright © 2022 Ertl https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Ertl, Hildegund C. J. Immunogenicity and toxicity of AAV gene therapy |
title | Immunogenicity and toxicity of AAV gene therapy |
title_full | Immunogenicity and toxicity of AAV gene therapy |
title_fullStr | Immunogenicity and toxicity of AAV gene therapy |
title_full_unstemmed | Immunogenicity and toxicity of AAV gene therapy |
title_short | Immunogenicity and toxicity of AAV gene therapy |
title_sort | immunogenicity and toxicity of aav gene therapy |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9411526/ https://www.ncbi.nlm.nih.gov/pubmed/36032092 http://dx.doi.org/10.3389/fimmu.2022.975803 |
work_keys_str_mv | AT ertlhildegundcj immunogenicityandtoxicityofaavgenetherapy |