DNA Nanotubule‐Based Nanodevices with ATP‐Responsive Gating for Direct Cytosolic Delivery of Nucleic Acids and Proteins
Abstract
Abstract Delivering biomacromolecules to the cytosol remains a formidable challenge, as these molecules are predominantly sequestered within endosomes after endocytosis. The limited efficacy of current delivery systems in promoting reliable endosomal escape underscores the need for innovative strategies. Here, we report a DNA origami nanotubule to construct transmembrane delivery nanodevices with size‐selective gating and ATP‐responsive channel activation. By integrating unilamellar vesicles as large storage compartments, these nanodevices can encapsulate a wide range of macromolecules, including small interfering RNA, messenger RNA, plasmid DNA, and CRISPR‐Cas9 ribonucleoprotein complexes. By bypassing traditional endocytic pathways, the nanotubules enable the delivery of substantial payload quantities directly across the plasma membrane. This approach provides a promising platform for delivering macromolecular therapeutics into the cytosol, advancing gene therapy strategies, and broadening their biomedical applications.
Article Details
Authors (10)
Di Gao
BLSA-ZJU Research Center and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China.
Ziqi Xu
Xiangli Li
State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical Engineering Nanjing University Nanjing 210023 China
Yuhan Zhao
Qianhao Min
Zixuan Chen
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry, School of Environment
Qin Xu
Ye Tian
Junpeng Xu
Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, P. R. China
Jun‐Jie Zhu
State Key Laboratory of Water Pollution Control and Green Resource Recycling State Key Laboratory of Analytical Chemistry for Life Science Frontiers Science Center for Critical Earth Material Cycling School of Environment School of Chemistry and Chemical Engineering Nanjing University Nanjing China