Laboratory for Biomolecular Nanotechnology. Department of Physics, Technical University of Munich, Am Coulombwall 4a, 85748 Garching, Germany.
Munich Institute of Biomedical Engineering, Technical University of Munich, Boltzmannstraße 11, 85748 Garching, Germany.
ACS Nano. 2022 Dec 27;16(12):20002-20009. doi: 10.1021/acsnano.1c11328. Epub 2022 Nov 2.
Effective broadband antiviral platforms that can act on existing viruses and viruses yet to emerge are not available, creating a need to explore treatment strategies beyond the trodden paths. Here, we report virus-encapsulating DNA origami shells that achieve broadband virus trapping properties by exploiting avidity and a widespread background affinity of viruses to heparan sulfate proteoglycans (HSPG). With a calibrated density of heparin and heparan sulfate (HS) derivatives crafted to the interior of DNA origami shells, we could encapsulate adeno, adeno-associated, chikungunya, dengue, human papilloma, noro, polio, rubella, and SARS-CoV-2 viruses or virus-like particles, in one and the same HS-functionalized shell system. Additional virus-type-specific binders were not needed for the trapping. Depending on the relative dimensions of shell to virus particles, multiple virus particles may be trapped per shell, and multiple shells can cover the surface of clusters of virus particles. The steric occlusion provided by the heparan sulfate-coated DNA origami shells can prevent viruses from further interactions with receptors, possibly including those found on cell surfaces.
目前尚无能够针对现有病毒和未来可能出现的病毒发挥作用的有效广谱抗病毒平台，因此需要探索超越传统途径的治疗策略。在这里，我们报告了一种病毒包裹的 DNA 折纸壳，它通过利用病毒对硫酸乙酰肝素蛋白聚糖 (HSPG) 的亲和力和广泛的背景亲和力来实现广谱病毒捕获特性。我们可以将腺病毒、腺相关病毒、基孔肯雅热病毒、登革热病毒、人乳头瘤病毒、诺如病毒、脊髓灰质炎病毒、风疹病毒和 SARS-CoV-2 病毒或病毒样颗粒封装在同一个具有 HS 功能化的壳系统中，该系统的内部具有经过校准的肝素和硫酸乙酰肝素 (HS) 衍生物密度。捕获不需要额外的针对特定病毒类型的结合物。根据壳与病毒颗粒的相对尺寸，每个壳可以捕获多个病毒颗粒，并且多个壳可以覆盖病毒颗粒簇的表面。由带硫酸乙酰肝素涂层的 DNA 折纸壳提供的空间位阻可以阻止病毒与受体进一步相互作用，这些受体可能包括细胞表面上的受体。
