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使用双特异性衔接蛋白实现溶瘤腺病毒的肿瘤靶向性

Tumor Targeting of Oncolytic Adenoviruses Using Bispecific Adapter Proteins.

作者信息

Niemann Julia, Kühnel Florian

机构信息

Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.

出版信息

Methods Mol Biol. 2020;2058:31-49. doi: 10.1007/978-1-4939-9794-7_3.

Abstract

Tumor-selectively replicating "oncolytic" adenoviruses based on serotype 5 are promising tools for the treatment of solid tumors. However, their effective delivery to the tumor by systemic administration remains challenging. Several strategies of molecular retargeting have been pursued to equip adenoviruses with molecular features that facilitate their efficient uptake by tumors and to protect healthy tissue from damage. Transductional retargeting can be conveniently achieved using bispecific molecular adapter proteins based on the ectodomain of the coxsackievirus and adenovirus receptor linked to tumor ligands of choice. In this chapter, we describe methods for their design, purification, and application.

摘要

基于5型血清型的肿瘤选择性复制“溶瘤”腺病毒是治疗实体瘤的有前景的工具。然而,通过全身给药将它们有效递送至肿瘤仍然具有挑战性。已经采用了几种分子重靶向策略,以使腺病毒具备有助于其被肿瘤有效摄取并保护健康组织免受损伤的分子特征。使用基于柯萨奇病毒和腺病毒受体胞外域并与所选肿瘤配体相连的双特异性分子衔接蛋白,可以方便地实现转导重靶向。在本章中,我们描述了其设计、纯化和应用方法。

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