Advances and future challenges in adenoviral vector pharmacology and targeting.
Advances and future challenges in adenoviral vector pharmacology and targeting.
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DOI：
10.2174/156652311796150363
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发表时间：
2011-08
影响因子：
3.6
通讯作者：
Barry MA
中科院分区：
文献类型：
--
作者：
Khare R;Chen CY;Weaver EA;Barry MA
腺病毒是一个强大的载体治疗应用，但它的使用是有限的，我们对其复杂的体内药理学的理解。在这篇综述中，我们描述了识别其与宿主的自然、广泛和多方面相互作用的必要性，因为这些信息对于有效地将病毒重定向到靶细胞至关重要。在载体的合理设计中，克服病毒“汇”序列的概念必须与重新靶向具有衣壳的目标群体以及保护载体免受预先存在或有毒免疫反应的影响相结合。还必须指出，大多数已知的腺病毒药理学是从最常用的血清型Ad5和Ad2推断出来的。然而，这些血清型可能不能代表所有的腺病毒，甚至可能不能代表对所有目的最有用的载体。Ad血清型之间的嵌合体可能在工程载体中变得有用，这些载体可以选择性地逃避大量的病毒陷阱，如Kupffer细胞，同时保留Ad5的健壮性。同样，对其他Ad血清型进行病媒化可能有助于完全避免对Ad5的免疫。综上所述，这项基础腺病毒生物学的研究对于开发更有策略地与宿主相互作用的载体以获得最佳治疗效果是必要的。
Adenovirus is a robust vector for therapeutic applications, but its use is limited by our understanding of its complex in vivo pharmacology. In this review we describe the necessity of identifying its natural, widespread, and multifaceted interactions with the host since this information will be crucial for efficiently redirecting virus into target cells. In the rational design of vectors, the notion of overcoming a sequence of viral “sinks” must be combined with re-targeting to target populations with capsid as well as shielding the vectors from pre-existing or toxic immune responses. It must also be noted that most known adenoviral pharmacology is deduced from the most commonly used serotypes, Ad5 and Ad2. However, these serotypes may not represent all adenoviruses, and may not even represent the most useful vectors for all purposes. Chimeras between Ad serotypes may become useful in engineering vectors that can selectively evade substantial viral traps, such as Kupffer cells, while retaining the robust qualities of Ad5. Similarly, vectorizing other Ad serotypes may become useful in avoiding immunity against Ad5 altogether. Taken together, this research on basic adenovirus biology will be necessary in developing vectors that interact more strategically with the host for the most optimal therapeutic effect.