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关于用于局部和全身基因治疗的纳米材料包被病毒载体的不断发展的经验教训。

Evolving lessons on nanomaterial-coated viral vectors for local and systemic gene therapy.

作者信息

Kasala Dayananda, Yoon A-Rum, Hong Jinwoo, Kim Sung Wan, Yun Chae-Ok

机构信息

Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, Republic of Korea.

Department of Pharmaceutics & Pharmaceutical Chemistry, Center for Controlled Chemical Delivery, University of Utah, Salt Lake City, UT 84112, USA.

出版信息

Nanomedicine (Lond). 2016 Jul;11(13):1689-713. doi: 10.2217/nnm-2016-0060. Epub 2016 Jun 27.

Abstract

Viral vectors are promising gene carriers for cancer therapy. However, virus-mediated gene therapies have demonstrated insufficient therapeutic efficacy in clinical trials due to rapid dissemination to nontarget tissues and to the immunogenicity of viral vectors, resulting in poor retention at the disease locus and induction of adverse inflammatory responses in patients. Further, the limited tropism of viral vectors prevents efficient gene delivery to target tissues. In this regard, modification of the viral surface with nanomaterials is a promising strategy to augment vector accumulation at the target tissue, circumvent the host immune response, and avoid nonspecific interactions with the reticuloendothelial system or serum complement. In the present review, we discuss various chemical modification strategies to enhance the therapeutic efficacy of viral vectors delivered either locally or systemically. We conclude by highlighting the salient features of various nanomaterial-coated viral vectors and their prospects and directions for future research.

摘要

病毒载体是癌症治疗中很有前景的基因载体。然而,由于病毒载体迅速扩散到非靶组织以及其免疫原性,病毒介导的基因疗法在临床试验中显示出治疗效果不足,导致在疾病部位的滞留不佳,并在患者中引发不良炎症反应。此外,病毒载体有限的靶向性妨碍了向靶组织的有效基因递送。在这方面,用纳米材料修饰病毒表面是一种很有前景的策略,可增强载体在靶组织的积累,规避宿主免疫反应,并避免与网状内皮系统或血清补体发生非特异性相互作用。在本综述中,我们讨论了各种化学修饰策略,以提高局部或全身递送的病毒载体的治疗效果。我们通过强调各种纳米材料包被的病毒载体的显著特征及其未来研究的前景和方向来进行总结。

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