Development of Novel Adenoviral Vectors to Overcome Challenges Observed With HAdV-5-based Constructs.
Development of Novel Adenoviral Vectors to Overcome Challenges Observed With HAdV-5-based Constructs.
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DOI：
10.1038/mt.2015.194
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发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Baker AH
中科院分区：
文献类型：
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作者：
Alonso-Padilla J;Papp T;Kaján GL;Benkő M;Havenga M;Lemckert A;Harrach B;Baker AH
在过去的二十年里，基于人5型腺病毒(HAdV-5)的重组载体在临床前模型和临床试验中得到了广泛的研究。然而，对HAdV-5与人类受试者相互作用的透彻了解揭示了人们对其产品适用性的主要担忧。高载体相关毒性和广泛的预先存在的免疫已被证明显著阻碍了HAdV-5介导的基因转移的有效性。因此，目前正在利用在HAdV-5工作中获得的深入知识来开发替代媒介。在这里，我们全面概述了近年来获得的数据，取消了HAdV-5载体系统基因传递的资格，以及正在寻求的新策略，以克服观察到的限制，特别强调正在进行的矢量化努力，以获得基于替代血清型的载体。
Recombinant vectors based on human adenovirus serotype 5 (HAdV-5) have been extensively studied in preclinical models and clinical trials over the past two decades. However, the thorough understanding of the HAdV-5 interaction with human subjects has uncovered major concerns about its product applicability. High vector-associated toxicity and widespread preexisting immunity have been shown to significantly impede the effectiveness of HAdV-5–mediated gene transfer. It is therefore that the in-depth knowledge attained working on HAdV-5 is currently being used to develop alternative vectors. Here, we provide a comprehensive overview of data obtained in recent years disqualifying the HAdV-5 vector for systemic gene delivery as well as novel strategies being pursued to overcome the limitations observed with particular emphasis on the ongoing vectorization efforts to obtain vectors based on alternative serotypes.