Adeno-associated viruses (AAV) and host immunity: a race between the hare and the hedgehog
Adeno-associated viruses (AAV) have emerged as the lead vector in clinical trials and form the basis for several approved gene therapies for human diseases, mainly owing to their ability to sustain robust and long-term in vivo transgene expression, their amenability to genetic engineering of cargo a...
Gespeichert in:
| Hauptverfasser: | , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
29 October 2021
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| In: |
Frontiers in immunology
Year: 2021, Jahrgang: 12, Pages: 1-25 |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2021.753467 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.3389/fimmu.2021.753467 Verlag, kostenfrei, Volltext: https://www.frontiersin.org/article/10.3389/fimmu.2021.753467 
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| Verfasserangaben: | Kleopatra Rapti and Dirk Grimm |
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| 520 | |a Adeno-associated viruses (AAV) have emerged as the lead vector in clinical trials and form the basis for several approved gene therapies for human diseases, mainly owing to their ability to sustain robust and long-term in vivo transgene expression, their amenability to genetic engineering of cargo and capsid, as well as their moderate toxicity and immunogenicity. Still, recent reports of fatalities in a clinical trial for a neuromuscular disease, although linked to an exceptionally high vector dose, have raised new caution about the safety of recombinant AAVs. Moreover, concerns linger about the presence of pre-existing anti-AAV antibodies in the human population, which precludes a significant percentage of patients from receiving, and benefitting from, AAV gene therapies. These concerns are exacerbated by observations of cellular immune responses and other adverse events, including detrimental off-target transgene expression in dorsal root ganglia. Here, we provide an update on our knowledge of the immunological and molecular race between AAV (the “hedgehog”) and its human host (the “hare”), together with a compendium of state-of-the-art technologies which provide an advantage to AAV and which, thus, promise safer and more broadly applicable AAV gene therapies in the future. | ||
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