Evolution of multivalent supramolecular assemblies of aptamers with target-defined spatial organization

IF 38.1 1区材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY

Nature nanotechnology Pub Date : 2025-06-06 DOI:10.1038/s41565-025-01939-8

Artem Kononenko, Vincenzo Caroprese, Yoan Duhoo, Cem Tekin, Maartje M. C. Bastings

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Abstract

Rapid identification of neutralizing molecules against new and mutating viruses is key to efficiently combating biorisk. Current binder identification techniques use a monovalent library of potential binders. Interestingly, proteins on pathogens are often homo-oligomeric—for example, the SARS-CoV-2 spike protein is a homotrimer. Here we describe a simple strategy, MEDUSA (multivalent evolved DNA-based supramolecular assembly), to evolve multivalent assemblies of aptamers with precise interligand spacing and three-fold symmetry, mirroring the geometric structure of many viral capsid proteins. MEDUSA allowed the selection of potent SARS-CoV-2 spike binders structurally distinct from any known aptamers. Decoupling the geometric and structural rigidity contributions toward selectivity made it possible to connect form to function, as demonstrated by the design of tunable fluorescent sensors. This approach offers a blueprint for targeting geometrically defined pathogen structures and developing rapid-response tools for emerging pathogens.

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具有目标定义空间组织的适体多价超分子组装的进化

快速识别针对新病毒和变异病毒的中和分子是有效对抗生物风险的关键。目前的结合剂鉴定技术使用潜在结合剂的单价库。有趣的是，病原体上的蛋白质通常是同源寡聚体——例如，SARS-CoV-2刺突蛋白是一种同源三聚体。在这里，我们描述了一种简单的策略，MEDUSA（多价进化的基于dna的超分子组装），进化出具有精确配体间距和三重对称性的多价适体组装，反映了许多病毒衣壳蛋白的几何结构。MEDUSA允许选择有效的SARS-CoV-2刺突结合物，其结构与任何已知的适体不同。解耦几何和结构刚性对选择性的贡献使得连接形式和功能成为可能，正如可调谐荧光传感器的设计所证明的那样。这种方法为针对几何定义的病原体结构和开发针对新出现病原体的快速反应工具提供了蓝图。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature nanotechnology 工程技术-材料科学：综合

CiteScore

59.70

自引率

0.80%

发文量

196

审稿时长

4-8 weeks

期刊介绍： Nature Nanotechnology is a prestigious journal that publishes high-quality papers in various areas of nanoscience and nanotechnology. The journal focuses on the design, characterization, and production of structures, devices, and systems that manipulate and control materials at atomic, molecular, and macromolecular scales. It encompasses both bottom-up and top-down approaches, as well as their combinations. Furthermore, Nature Nanotechnology fosters the exchange of ideas among researchers from diverse disciplines such as chemistry, physics, material science, biomedical research, engineering, and more. It promotes collaboration at the forefront of this multidisciplinary field. The journal covers a wide range of topics, from fundamental research in physics, chemistry, and biology, including computational work and simulations, to the development of innovative devices and technologies for various industrial sectors such as information technology, medicine, manufacturing, high-performance materials, energy, and environmental technologies. It includes coverage of organic, inorganic, and hybrid materials.