Zeng, Yang C. Young, Olivia J. Wintersinger, Christopher M. Anastassacos, Frances M. MacDonald, James I. Isinelli, Giorgia Dellacherie, Maxence O. Sobral, Miguel Bai, Haiqing Graveline, Amanda R. Vernet, Andyna Sanchez, Melinda Mulligan, Kathleen Choi, Youngjin Ferrante, Thomas C. Keskin, Derin B. Fell, Geoffrey G. Neuberg, Donna Wu, Catherine J. Mooney, David J. Kwon, Ick Chan Ryu, Ju Hee Shih, William M. 2024-05-13T02:00:16Z 2024-05-13T02:00:16Z 2024-05-13 2024-07 1748-3387 https://pubs.kist.re.kr/handle/201004/149822 Multivalent presentation of ligands often enhances receptor activation and downstream signalling. DNA origami offers a precise nanoscale spacing of ligands, a potentially useful feature for therapeutic nanoparticles. Here we use a square-block DNA origami platform to explore the importance of the spacing of CpG oligonucleotides. CpG engages Toll-like receptors and therefore acts to activate dendritic cells. Through in vitro cell culture studies and in vivo tumour treatment models, we demonstrate that square blocks induce Th1 immune polarization when CpG is spaced at 3.5 nm. We observe that this DNA origami vaccine enhances DC activation, antigen cross-presentation, CD8 T-cell activation, Th1-polarized CD4 activation and natural-killer-cell activation. The vaccine also effectively synergizes with anti-PD-L1 for improved cancer immunotherapy in melanoma and lymphoma models and induces long-term T-cell memory. Our results suggest that DNA origami may serve as a platform for controlling adjuvant spacing and co-delivering antigens in vaccines. The spacing of ligands presented to cells can have a huge impact on cellular responses. DNA origami is used to block structures to control the distribution of Toll-like receptor ligands and optimize presentation in the activation of dendritic cells in cancer immunotherapy. English Nature Publishing Group Fine tuning of CpG spatial distribution with DNA origami for improved cancer vaccination Article 10.1038/s41565-024-01615-3 1 Nature Nanotechnology, v.19, no.7, pp.1055 - 1065 Nature Nanotechnology 19 7 1055 1065 N scie scopus 001185506500001 2-s2.0-85187878771 Nanoscience & Nanotechnology Materials Science, Multidisciplinary Science & Technology - Other Topics Materials Science Article FOLDING DNA RECEPTOR TLR9 NANOPARTICLES ACTIVATION SHAPES IMMUNE-RESPONSES DENDRITIC CELLS