Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by National Cancer Institute, Frederick, Maryland.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2021 Jan;13(1):e1657. doi: 10.1002/wnan.1657. Epub 2020 Jul 15.
Gene therapeutics including siRNAs, anti-sense oligos, messenger RNAs, and CRISPR ribonucleoprotein complexes offer unmet potential to treat over 7,000 known genetic diseases, as well as cancer, through targeted in vivo modulation of aberrant gene expression and immune cell activation. Compared with viral vectors, nonviral delivery vectors offer controlled immunogenicity and low manufacturing cost, yet suffer from limitations in toxicity, targeting, and transduction efficiency. Structured DNA assemblies fabricated using the principle of scaffolded DNA origami offer a new nonviral delivery vector with intrinsic, yet controllable immunostimulatory properties and virus-like spatial presentation of ligands and immunogens for cell-specific targeting, activation, and control over intracellular trafficking, in addition to low manufacturing cost. However, the relative utilities and limitations of these vectors must clearly be demonstrated in preclinical studies for their clinical potential to be realized. Here, we review the major capabilities, opportunities, and challenges we foresee in translating these next-generation delivery and vaccine vectors to the clinic. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.
基因治疗包括 siRNA、反义寡核苷酸、信使 RNA 和 CRISPR 核糖核蛋白复合物，通过靶向体内调节异常基因表达和免疫细胞激活，为治疗 7000 多种已知遗传疾病以及癌症提供了未满足的潜力。与病毒载体相比，非病毒递送载体具有可控的免疫原性和低制造成本，但存在毒性、靶向性和转导效率方面的限制。使用支架 DNA 折纸原理制造的结构化 DNA 组装体提供了一种新型非病毒递送载体，具有内在的、但可控制的免疫刺激性特性，以及类似病毒的配体和免疫原的空间呈现，用于细胞特异性靶向、激活和控制细胞内运输，此外还具有低制造成本。然而，为了实现其临床潜力，这些载体的相对效用和局限性必须在临床前研究中得到明确证明。在这里，我们综述了我们预见的将这些下一代递药和疫苗载体转化为临床应用的主要能力、机遇和挑战。本文属于以下类别：治疗方法和药物发现 > 新兴技术 仿生纳米材料 > 基于核酸的结构 治疗方法和药物发现 > 用于肿瘤疾病的纳米医学。
