Long Single‐Stranded DNA with Site‐Specific Modifications to Enable Single‐Base‐Resolution Epigenetics

C Chenyou Zhu (Department of Chemistry) Y Yin Xu Z Ziyang Hao (School of Pharmaceutical Sciences) Y Yuan Zhuang (Department of Chemistry) R Rui Xu (College & Hospital of Stomatology) Y Yufan Pan (Department of Chemistry) J Jiezhong Shi (Engineering Research Center of Advanced Rare Earth Materials (Ministry of Education) Department of Chemistry Tsinghua University Beijing 100084 P.R. China) Y Yujie Li (Engineering Research Center of Advanced Rare Earth Materials (Ministry of Education), Department of Chemistry) Y Yifan Jiang (Micro−Nano Engineering Sciences Research Center, School of Mechanical Engineering) T Tianran Wang Y Yuhe R. Yang (CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety CAS Key Laboratory of Nanosystem and Hierarchical Fabrication CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing P.R. China) H Huajie Liu (School of Chemical Science and Engineering Shanghai Research Institute for Intelligent Autonomous Systems Key Laboratory of Advanced Civil Engineering Materials of Ministry of Education Tongji University Shanghai 200092 P.R. China) D Dali Han Y Yuanchen Dong (CAS Key Laboratory of Colloid Interface and Chemical Thermodynamics, Beijing National Laboratory for Molecular Sciences, Institute of Chemistry) C Chuan He D Dongsheng Liu (Department of Chemistry)

Abstract

Abstract We report a method for synthesizing site‐specifically modified long single‐stranded DNA (ssDNA) with high purity and fidelity. With the successful synthesis of long ssDNA carrying different 5‐methylcytosine (5mC) patterns, single‐base‐resolution analysis of 5mC epigenetic dynamics at specific genomic loci were enabled in mammalian cells. The results revealed that the density of 5mC sites synergistically correlated with their maintenance. This study opens new avenues for precise epigenetic manipulation and therapeutic applications.

Article Details

Volume / Issue Vol. 65, Issue 3
Published January 16, 2026
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (16)

C

Chenyou Zhu

Department of Chemistry

Y

Yin Xu

Z

Ziyang Hao

School of Pharmaceutical Sciences

Y

Yuan Zhuang

Department of Chemistry

R

Rui Xu

College & Hospital of Stomatology

Y

Yufan Pan

Department of Chemistry

J

Jiezhong Shi

Engineering Research Center of Advanced Rare Earth Materials (Ministry of Education) Department of Chemistry Tsinghua University Beijing 100084 P.R. China

Y

Yujie Li

Engineering Research Center of Advanced Rare Earth Materials (Ministry of Education), Department of Chemistry

Y

Yifan Jiang

Micro−Nano Engineering Sciences Research Center, School of Mechanical Engineering

T

Tianran Wang

Y

Yuhe R. Yang

CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety CAS Key Laboratory of Nanosystem and Hierarchical Fabrication CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing P.R. China

H

Huajie Liu

School of Chemical Science and Engineering Shanghai Research Institute for Intelligent Autonomous Systems Key Laboratory of Advanced Civil Engineering Materials of Ministry of Education Tongji University Shanghai 200092 P.R. China

D

Dali Han

Y

Yuanchen Dong

CAS Key Laboratory of Colloid Interface and Chemical Thermodynamics, Beijing National Laboratory for Molecular Sciences, Institute of Chemistry

C

Chuan He

D

Dongsheng Liu

Department of Chemistry