Locked Nucleic Acid Modification for Base‐Stacking Engineering of Self‐Assembled DNA Crystals
Abstract
Abstract DNA hybridization and assembly processes are governed by the concerted effects of Watson–Crick pairing and base‐stacking interactions. While sequence engineering and chemical modifications have been extensively exploited to regulate DNA hybridization processes and complex structural assembly of DNA, here we demonstrate the use of locked nucleic acid (LNA) modifications to finely tune base‐stacking interactions, which are yet to be explored in DNA assembly processes, to program the growth of self‐assembled DNA crystals. We find that sticky‐end LNA modifications decrease base‐pair spacing and enhance base‐stacking energy, which synergistically improves interstrand affinity and accelerates hybridization rate constants, as revealed by strand displacement kinetics, molecular dynamics simulations, and small‐angle X‐ray scattering analysis. This LNA‐based base‐stacking engineering strategy can finely tune base‐stacking energy landscapes to drive anisotropic growth and morphological control in self‐assembled DNA crystal. We further establish a quantitative framework for probing structure–energy relationships in base‐stacking interactions, which not only paves the way for better control of structural DNA nanotechnology but also provides mechanistic insights for developing dynamic DNA nanosystems.
Article Details
Authors (14)
Jielin Chen
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, Zhang Jiang Institute for Advanced Study and National Center for Translational Medicine, Shanghai Jiao Tong University
Mingqiang Li
State Key Laboratory of Synergistic Chem-Bio Synthesis, State Key Laboratory of Micro-Nano Engineering Science, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, Zhangjiang Institute for Advanced Study, and National Center for Translational Medicine
Ziyu Li
Yuqing Tang
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Institute of Translational Medicine, Shanghai Jiao Tong University
Hanwei Zhang
Jianing Cheng
Zheze Dai
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Institute of Translational Medicine, Shanghai Jiao Tong University
Xiaolei Zuo
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acids Chemistry and Nanomedicine, Renji Hospital, School of Medicine
Qian Li
Fei Wang
Sisi Jia
Zhangjiang Laboratory
Hui Lv
Institute of Materiobiology, College of Sciences
Chunhai Fan
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, Zhang Jiang Institute for Advanced Study and National Center for Translational Medicine
Xiaoguo Liu
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, Zhangjiang Institute for Advanced Study and National Center for Translational Medicine