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病毒载体介导的 RNA 干扰在癌症治疗中的最佳传递。

Optimal delivery of RNA interference by viral vectors for cancer therapy.

机构信息

Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.

Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.

出版信息

Mol Ther. 2023 Nov 1;31(11):3127-3145. doi: 10.1016/j.ymthe.2023.09.012. Epub 2023 Sep 20.

Abstract

In recent years, there has been a surge in the innovative modification and application of the viral vector-based gene therapy field. Significant and consistent improvements in the engineering, delivery, and safety of viral vectors have set the stage for their application as RNA interference (RNAi) delivery tools. Viral vector-based delivery of RNAi has made remarkable breakthroughs in the treatment of several debilitating diseases and disorders (e.g., neurological diseases); however, their novelty has yet to be fully applied and utilized for the treatment of cancer. This review highlights the most promising and emerging viral vector delivery tools for RNAi therapeutics while discussing the variables limiting their success and suitability for cancer therapy. Specifically, we outline different integrating and non-integrating viral platforms used for gene delivery, currently employed RNAi targets for anti-cancer effect, and various strategies used to optimize the safety and efficacy of these RNAi therapeutics. Most importantly, we provide great insight into what challenges exist in their application as cancer therapeutics and how these challenges can be effectively navigated to advance the field.

摘要

近年来,基于病毒载体的基因治疗领域的创新性修饰和应用呈爆炸式增长。病毒载体的工程、传递和安全性的显著和持续改进为其作为 RNA 干扰 (RNAi) 传递工具的应用奠定了基础。基于病毒载体的 RNAi 传递在治疗几种使人衰弱的疾病和病症(如神经疾病)方面取得了显著突破;然而,它们的新颖性尚未得到充分应用和利用来治疗癌症。本综述重点介绍了最有前途和新兴的病毒载体 RNAi 治疗传递工具,同时讨论了限制其成功和适用于癌症治疗的变量。具体来说,我们概述了用于基因传递的不同整合和非整合病毒平台、目前用于抗癌效果的 RNAi 靶点,以及用于优化这些 RNAi 治疗剂的安全性和疗效的各种策略。最重要的是,我们深入了解了它们作为癌症治疗剂的应用中存在的挑战,以及如何有效地应对这些挑战来推动该领域的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fb4/10638062/ac6e123d6201/fx1.jpg

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