Department of Biosciences, School of Natural Sciences and Munich Institute of Biomedical Engineering, Technical University of Munich, Boltzmannstraße 11, 85748 Garching, Germany.
Institute of Virology, School of Medicine & Health, Technical University of Munich and Helmholtz Munich, Trogerstraße 30, 81675 Munich, Germany.
ACS Appl Mater Interfaces. 2024 May 22;16(20):25836-25842. doi: 10.1021/acsami.4c03700. Epub 2024 May 10.
We demonstrate the use of DNA origami to create virus-trapping nanoshells that efficiently neutralize hepatitis B virus (HBV) in cell culture. By modification of the shells with a synthetic monoclonal antibody that binds to the HBV envelope, the effective neutralization potency per antibody is increased by approximately 100 times compared to using free antibodies. The improvements in neutralizing the virus are attributed to two factors: first, the shells act as a physical barrier that blocks the virus from interacting with host cells; second, the multivalent binding of the antibodies inside the shells lead to stronger attachment to the trapped virus, a phenomenon known as avidity. Pre-incubation of shells with HBV and simultaneous addition of both components separately to cells lead to comparable levels of neutralization, indicating rapid trapping of the virions by the shells. Our study highlights the potential of the DNA shell system to rationally create antivirals using components that, when used individually, show little to no antiviral effectiveness.
我们展示了 DNA 折纸术在制造病毒陷阱纳米壳中的应用，这些纳米壳可有效中和细胞培养中的乙型肝炎病毒 (HBV)。通过用与 HBV 包膜结合的合成单克隆抗体修饰壳，可以将每个抗体的有效中和效力提高约 100 倍，而不是使用游离抗体。提高中和病毒的效果归因于两个因素：首先，壳作为物理屏障，阻止病毒与宿主细胞相互作用；其次，壳内抗体的多价结合导致与捕获病毒的更强附着，这种现象称为亲和力。壳与 HBV 的预孵育以及同时将两种成分分别添加到细胞中导致相当水平的中和，表明壳快速捕获病毒粒子。我们的研究强调了 DNA 壳系统的潜力，可以使用单独使用时几乎没有抗病毒效果的组件，合理地制造抗病毒药物。
