Morphology Dictated Immune Activation with Framework Nucleic Acids

Author:

Hu Yao1,Luo Zhongxu1,Ge Zhilei2,Li Qian2,Yang Peihui1,Zhang Honglu3ORCID,Zhang Huan4

Affiliation:

1. Department of Chemistry College of Chemistry and Materials Science Jinan University Guangzhou 511443 China

2. School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine Shanghai Jiao Tong University Shanghai 200240 China

3. School of Biomedical Sciences and Engineering South China University of Technology Guangzhou International Campus Guangzhou 511442 China

4. School of Agriculture and Biology Shanghai Jiao Tong University Shanghai 200240 China

Abstract

AbstractFramework nucleic acids (FNAs) of various morphologies, designed using the precise and programmable Watson‐Crick base pairing, serve as carriers for biomolecule delivery in biology and biomedicine. However, the impact of their shape, size, concentration, and the spatial presentation of cytosine‐phosphate‐guanine oligodeoxynucleotides (CpG ODNs) on immune activation remains incompletely understood. In this study, representative FNAs with varying morphologies are synthesized to explore their immunological responses. Low concentrations (50 nM) of all FNAs elicited no immunostimulation, while high concentrations of elongated DNA nanostrings and tetrahedrons triggered strong activation due to their larger size and increased cellular uptake, indicating that the innate immune responses of FNAs depend on both dose and morphology. Notably, CpG ODNs' immune response can be programmed by FNAs through regulating the spatial distance, with optimal spacing of 7‐8 nm eliciting the highest immunostimulation. These findings demonstrate FNAs' potential as a designable tool to study nucleic acid morphology's impact on biological responses and provide a strategy for future CpG‐mediated immune activation carrier design.

Funder

National Natural Science Foundation of China

Publisher

Wiley

Subject

Biomaterials,Biotechnology,General Materials Science,General Chemistry

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