With numerous recent advances, the field of therapeutic nucleic acid nanotechnology is now poised for clinical translation supported by several examples of FDA-approved nucleic acid nanoformulations including two recent mRNA-based COVID-19 vaccines. Within this rapidly growing field, a new subclass of nucleic acid therapeutics called nucleic acid nanoparticles (NANPs) has emerged in recent years, which offers several unique properties distinguishing it from traditional therapeutic nucleic acids. Key unique aspects of NANPs include their well-defined 3D structure, their tunable multivalent architectures, and their ability to incorporate conditional activations of therapeutic targeting and release functions that enable diagnosis and therapy of cancer, regulation of blood coagulation disorders, as well as the development of novel vaccines, immunotherapies, and gene therapies. However, non-consolidated research developments of this highly interdisciplinary field create crucial barriers that must be overcome in order to impact a broader range of clinical indications. Forming a consortium framework for nucleic acid nanotechnology would prioritize and consolidate translational efforts, offer several unifying solutions to expedite their transition from bench-to-bedside, and potentially decrease the socio-economic burden on patients for a range of conditions. Herein, we review the unique properties of NANPs in the context of therapeutic applications and discuss their associated translational challenges.

随着近期的众多进展，治疗性核酸纳米技术领域现已准备好进行临床转化，并得到 FDA 批准的核酸纳米制剂的几个例子的支持，包括最近的两种基于 mRNA 的 COVID-19 疫苗。在这个快速发展的领域中，近年来出现了一种新的核酸治疗亚类，称为核酸纳米粒子（NANP），它具有多种区别于传统治疗性核酸的独特特性。 NANP 的关键独特之处包括其明确的 3D 结构、可调节的多价架构，以及整合治疗靶向和释放功能的条件激活的能力，从而能够诊断和治疗癌症、调节凝血障碍以及开发新型疫苗、免疫疗法和基因疗法。然而，这一高度跨学科领域的非综合研究发展造成了必须克服的关键障碍，才能影响更广泛的临床适应症。形成核酸纳米技术联盟框架将优先考虑和巩固转化工作，提供几种统一的解决方案以加快其从实验室到临床的过渡，并有可能减轻一系列疾病患者的社会经济负担。在此，我们回顾了 NANP 在治疗应用中的独特性质，并讨论了其相关的转化挑战。