Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer.
Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer.
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DOI：
10.1007/s40259-023-00585-7
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发表时间：
2023-05
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重组腺相关病毒（AAV）已经成为有前途的基因递送载体，导致三个美国食品和药物管理局（FDA）和一个欧洲药品管理局（EMA）批准的基于AAV的基因疗法。尽管在一些临床试验中是治疗性基因转移的领先平台，但针对AAV载体和转基因的宿主免疫应答阻碍了其广泛应用。多种因素，包括载体设计、剂量和施用途径，有助于AAV的总体免疫原性。针对AAV衣壳和转基因的免疫应答涉及初始先天感应。先天免疫应答随后触发适应性免疫应答以引发针对AAV载体的稳健和特异性应答。AAV基因治疗的临床试验和临床前研究提供了关于与AAV相关的免疫介导的毒性的重要信息，但研究表明临床前模型无法精确预测人类基因递送的结果。这篇综述讨论了对AAV的先天性和适应性免疫反应的贡献，突出了减轻这些反应的挑战和潜在策略，从而提高AAV基因治疗的治疗潜力。
Recombinant adeno-associated viruses (AAVs) have emerged as promising gene delivery vehicles resulting in three US Food and Drug Administration (FDA) and one European Medicines Agency (EMA)-approved AAV-based gene therapies. Despite being a leading platform for therapeutic gene transfer in several clinical trials, host immune responses against the AAV vector and transgene have hampered their widespread application. Multiple factors, including vector design, dose, and route of administration, contribute to the overall immunogenicity of AAVs. The immune responses against the AAV capsid and transgene involve an initial innate sensing. The innate immune response subsequently triggers an adaptive immune response to elicit a robust and specific response against the AAV vector. AAV gene therapy clinical trials and preclinical studies provide important information about the immune-mediated toxicities associated with AAV, yet studies suggest preclinical models fail to precisely predict the outcome of gene delivery in humans. This review discusses the contribution of the innate and adaptive immune response against AAVs, highlighting the challenges and potential strategies to mitigate these responses, thereby enhancing the therapeutic potential of AAV gene therapy.
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DOI：
10.1016/j.omtm.2021.10.010
发表时间：
2021-12-10
期刊：
Molecular therapy. Methods & clinical development
影响因子：
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作者：
Arjomandnejad M;Sylvia K;Blackwood M;Nixon T;Tang Q;Muhuri M;Gruntman AM;Gao G;Flotte TR;Keeler AM
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影响因子：
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作者：
Butterfield, John S. S.;Biswas, Moanaro;Herzog, Roland W.
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Herzog, Roland W.
影响因子：
4.6
作者：
Bertin, Berangere;Veron, Philippe;Mingozzi, Federico
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Mingozzi, Federico
DOI：
10.1073/pnas.0904514106
发表时间：
2009-09-22
影响因子：
11.1
作者：
Brantly, Mark L.;Chulay, Jeffrey D.;Flotte, Terence R.
通讯作者：
Flotte, Terence R.
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影响因子：
7.3
作者：
Bertolini TB;Shirley JL;Zolotukhin I;Li X;Kaisho T;Xiao W;Kumar SRP;Herzog RW
通讯作者：
Herzog RW