류주희 (Harvard Medical School, 한국과학기술연구원) | 한빛사논문 > 한빛사

한빛사논문

조회1,025

Harvard Medical School, 한국과학기술연구원

CV File

Nat. Nanotechnol., Mar 15 2024, | https://doi.org/10.1038/s41565-024-01615-3 Fine tuning of CpG spatial distribution with DNA origami for improved cancer vaccination

Yang C. Zeng ^1,2,3, Olivia J. Young ^1,2,3,4, Christopher M. Wintersinger ^1,3, Frances M. Anastassacos ^2,3, James I. MacDonald ², Giorgia Isinelli ^2,5, Maxence O. Dellacherie ⁶, Miguel Sobral ⁶, Haiqing Bai ², Amanda R. Graveline ², Andyna Vernet ², Melinda Sanchez ², Kathleen Mulligan ¹, Youngjin Choi ⁷, Thomas C. Ferrante ², Derin B. Keskin ⁸, Geoffrey G. Fell ⁹, Donna Neuberg ⁹, Catherine J. Wu ⁸, David J. Mooney ^2,6, Ick Chan Kwon ^1,7,10, Ju Hee Ryu ^1,7,*& William M. Shih ^1,2,3,*

¹Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
²Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
³Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
⁴Harvard-Massachusetts Institute of Technology (MIT) Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁵Department of Drug and Health Sciences, University of Catania, Catania, Italy.
⁶Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
⁷Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.
⁸Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁹Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.
¹⁰KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea.

^*Corresponding authors: correspondence to Ju Hee Ryu or William M. Shih

Abstract

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.

논문정보