基于纳米平台的癌症治疗体内基因传递系统。

Nanoplatform-Based In Vivo Gene Delivery Systems for Cancer Therapy.

机构信息

Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.

出版信息

Small. 2024 Jul;20(30):e2312153. doi: 10.1002/smll.202312153. Epub 2024 Mar 5.

Abstract

Gene therapy uses modern molecular biology methods to repair disease-causing genes. As a burgeoning therapeutic, it has been widely applied for cancer therapy. Since 1989, there have been numerous clinical gene therapy cases worldwide. However, a few are successful. The main challenge of clinical gene therapy is the lack of efficient and safe vectors. Although viral vectors show high transfection efficiency, their application is still limited by immune rejection and packaging capacity. Therefore, the development of non-viral vectors is overwhelming. Nanoplatform-based non-viral vectors become a hotspot in gene therapy. The reasons are mainly as follows. 1) Non-viral vectors can be engineered to be uptaken by specific types of cells or tissues, providing effective targeting capability. 2) Non-viral vectors can protect goods that need to be delivered from degradation. 3) Nanoparticles can transport large-sized cargo such as CRISPR/Cas9 plasmids and nucleoprotein complexes. 4) Nanoparticles are highly biosafe, and they are not mutagenic in themselves compared to viral vectors. 5) Nanoparticles are easy to scale preparation, which is conducive to clinical conversion and application. Here, an overview of the categories of nanoplatform-based non-viral gene vectors, the limitations on their development, and their applications in cancer therapy.

摘要

基因治疗利用现代分子生物学方法修复致病基因。作为一种新兴的治疗方法,它已被广泛应用于癌症治疗。自 1989 年以来,全球已有众多临床基因治疗案例。然而,成功的案例却寥寥无几。临床基因治疗的主要挑战是缺乏高效和安全的载体。虽然病毒载体具有较高的转染效率,但由于免疫排斥和包装容量的限制,其应用仍受到限制。因此,非病毒载体的发展势不可挡。基于纳米平台的非病毒载体成为基因治疗的热点。主要原因如下。1)非病毒载体可以被设计为被特定类型的细胞或组织摄取,从而提供有效的靶向能力。2)非病毒载体可以保护需要输送的货物免受降解。3)纳米颗粒可以输送 CRISPR/Cas9 质粒和核蛋白复合物等大型货物。4)与病毒载体相比,纳米颗粒具有高度的生物安全性,本身不具有致突变性。5)纳米颗粒易于规模化制备,有利于临床转化和应用。本文概述了基于纳米平台的非病毒基因载体的类别、其发展的局限性以及它们在癌症治疗中的应用。

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