Exploring the functions of polymers in adenovirus-mediated gene delivery: Evading immune response and redirecting tropism
Exploring the functions of polymers in adenovirus-mediated gene delivery: Evading immune response and redirecting tropism
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探索聚合物在腺病毒介导的基因传递中的功能：逃避免疫反应和重定向趋向性
DOI：
10.1016/j.actbio.2019.06.059
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发表时间：
2019
影响因子：
9.7
通讯作者：
Gao Zibin
中科院分区：
文献类型：
--
作者：
Sun Yanping;Lv Xiaoqian;Ding Pingtian;Wang Long;Sun Yongjun;Li Shuo;Zhang Huimin;Gao Zibin
腺病毒（Ad）由于其独特的属性，在基因治疗中成为一种很有前途的病毒载体。然而，Ad载体的临床应用目前受到其免疫原性和广泛的天然性的限制。为了解决这些障碍，各种非免疫原性聚合物被用于化学或物理修饰Ad载体。本文从逃避宿主对Ad的免疫反应和重定向Ad向性两个方面系统地讨论了聚合物在Ad介导的基因传递中的功能。以聚乙二醇（PEG）为首，各种聚合物已被开发用于屏蔽Ad载体的表面，并很好地逃避宿主免疫反应，阻断car依赖的细胞摄取，并减少在肝脏中的积累。此外，用靶向聚合物（包括靶向配体共轭聚合物和生物响应聚合物）屏蔽Ad载体也可以有效地将Ad载体重新靶向到肿瘤组织，减少其在非靶向组织中的分布。由于具有逃避免疫反应和重新靶向Ad载体的潜力，聚合物修饰被普遍认为是促进Ad载体在病毒治疗中的临床应用的一种有前途的策略。毫无疑问，腺病毒（Ads）是极具吸引力的基因治疗载体，它在克服细胞外和细胞内屏障方面具有高度的复杂性和有效性，这是任何其他非病毒基因载体都无法超越的。不幸的是，它们的临床应用仍然受到一些关键障碍的限制，包括免疫原性和天然广泛性。因此，从不同角度开发了各种优雅的策略来解决这些障碍。在这些策略中，非免疫原性聚合物涂层广告引起了人们的广泛关注。本文从逃避宿主对Ad的免疫反应和重定向Ad向性两个方面系统地讨论了聚合物在Ad介导的基因传递中的功能。此外，本文还对聚合物修饰Ad的关键因素进行了总结，为设计更有效、更安全的聚合物-Ad杂交基因载体提供理论指导。
Adenovirus (Ad) is a promising viral carrier in gene therapy because of its unique attribution. However, clinical applications of Ad vectors are currently restricted by their immunogenicity and broad native tropism. To address these obstacles, a variety of nonimmunogenic polymers are utilized to modify Ad vectors chemically or physically. In this review, we systemically discuss the functions of polymers in Ad-mediated gene delivery from two aspects: evading the host immune responses to Ads and redirecting Ad tropism. With polyethylene glycol (PEG) first in order, a variety of polymers have been developed to shield the surface of Ad vectors and well accomplished to evade the host immune response, block CAR-dependant cellular uptake, and reduce accumulation in the liver. In addition, shielding Ad vectors with targeted polymers (including targeting ligand-conjugated polymers and bio-responsive polymers) can also efficiently retarget Ad vectors to tumor tissues and reduce their distribution in nontargeted tissues. With its potential to evade the immune response and retarget Ad vectors, modification with polymers has been generally regarded as a promising strategy to facilitate the clinical applications of Ad vectors for virotherapy.Statement of SignificanceThere is no doubt that Adenovirus (Ads) are attractive vectors for gene therapy, with high sophistication and effectiveness in overcoming both extra- and intracellular barriers, which cannot be exceeded by any other nonviral gene vectors. Unfortunately, their clinical applications are still restricted by some critical hurdles, including immunogenicity and native broad tropism. Therefore, a variety of elegant strategies have been developed from various angles to address these hurdles. Among these various strategies, coating Ads with nonimmunogenic polymers has attracted much attention. In this review, we systemically discuss the functions of polymers in Ad-mediated gene delivery from two aspects: evading the host immune responses to Ads and redirecting Ad tropism. In addition, the key factors in Ad modification with polymers have been highlighted and summarized to provide guiding theory for the design of more effective and safer polymer-Ad hybrid gene vectors.