DNA Nanotechnology-Endowed Synthetic Immunology

Abstract

Synthetic immunology merges synthetic biology and immunology, offering a new paradigm to unravel complex immune mechanisms and address major diseases. Unlike traditional ligand display platforms that face inherent limitations, DNA nanotechnology provides unparalleled programmability and nanoscale precision, enabling the fine-tuning of key immune parameters like ligand valence state and spatial distribution, as well as receptor-ligand interaction. This review covers recent advances in DNA nanotechnology for immune modulation, highlighting its role in the programmable design of immune responses. We first outline how DNA-based tools facilitate precise interrogation of immune cell mechanics, including receptor-ligand dynamics, ligand spatial arrangement, and mechanotransduction. We then discuss the applications in immune cell engineering, focusing on receptor reprogramming and surface functionalization, through customizable DNA scaffolds that reconfigure cellular communication. The modular nature of DNA nanotechnology further underpins the development of artificial immune cells, bridging synthetic biology with immunotherapy. In addition, we highlight emerging frontiers such as heterogenous multivalent ligand synergy and DNA-based synthetic cells, poised to expand mechanistic insights and therapeutic innovation. By integrating bottom-up design with top-down cellular interventions, DNA nanotechnology establishes a transformative framework for synthetic immunology, providing innovative solutions to fundamental and clinical challenges in immune regulation.

Keywords

Synthetic immunology / DNA nanotechnology / Protein engineering / Immune regulation / Nucleic acids / Immune biophysics / Immunotherapy / Artificial cell

RIGHTS & PERMISSIONS

2025 SIOC, CAS, Shanghai, & WILEY-VCH GmbH