Opportunities and challenges for the clinical translation of structured DNA assemblies as gene therapeutic delivery and vaccine vectors.
Opportunities and challenges for the clinical translation of structured DNA assemblies as gene therapeutic delivery and vaccine vectors.
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DOI：
10.1002/wnan.1657
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Bathe M
中科院分区：
文献类型：
--
作者：
Dobrovolskaia MA;Bathe M
包括 siRNA、反义寡核苷酸、信使 RNA 和 CRISPR 核糖核蛋白复合物在内的基因疗法通过体内靶向调节异常基因表达和免疫细胞激活，为治疗 7,000 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较低的制造成本，但在毒性、靶向性和转导效率方面受到限制。使用支架式 DNA 折纸原理制造的结构化 DNA 组件提供了一种新的非病毒递送载体，其具有内在但可控的免疫刺激特性，以及配体和免疫原的类病毒空间呈现，用于细胞特异性靶向、激活和控制细胞内运输，此外制造成本较低。然而，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，才能实现其临床潜力。在这里，我们回顾了我们预见到的将这些下一代递送和疫苗载体转化为临床的主要能力、机遇和挑战。本文分类为：治疗方法和药物发现 > 新兴技术生物启发的纳米材料 > 基于核酸的结构治疗方法和药物发现 > 肿瘤疾病的纳米医学 病毒样核酸纳米粒子可以单独或组合地递送和释放 CRISPR RNP、HDR 模板和 siRNA，用于下一代体内基因治疗应用。
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 Virus‐like nucleic acid nanoparticles can be programmed to deliver and release CRISPR RNPs, HDR templates, and siRNAs either alone, or in combination, for next‐generation in vivo gene therapeutic applications.
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