A worm-like nucleic acid nanostructure for gene delivery and endosomal escape via ClC3 ion exchanger

Science Advances 2026 Open access

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Authors: Yu Xiao, Cecilia Ka Wing Chan, Leo Kit Cheung Lee, Moldir Shyngys, Yee Ting Elaine Chiu, Evelyn Y. Xue, Kathy Oi-lan Lui, Ho Yin Edwin Chan, Sharon Shui Yee Leung, Xiaoqiang Yao, Chung Hang Jonathan Choi
DOI: 10.1126/sciadv.adw0891
Cited by: 2
References: 169

Abstract

Nanoparticle-based gene delivery can enable therapeutic applications with lower cytotoxicity than viral vectors, but its efficacy is often hampered by endosomal entrapment. We present a nucleic acid nanotechnology approach to circumvent this delivery bottleneck by adsorbing therapeutic nucleic acids (DNA, small interfering RNA, microRNA, or messenger RNA) to a gold-polydopamine nanoworm template, thereby assembling a three-dimensional worm-like nucleic acid nanostructure. Devoid of cationic groups, lipids, or mechanical stimuli, this nanostructure naturally activates the chloride voltage-gated channel 3 (ClC3) ion exchanger in endosomes given its worm-like shape; in turn, ClC3 mediates endosomal H + and Cl − accumulation and eventual membrane rupture for cytosolic release, contributing to robust endosomal escape with a correlation coefficient

Fields of Study & Subjects

RNA Interference and Gene Delivery Nanopore and Nanochannel Transport Studies Advanced biosensing and bioanalysis techniques

Publication details

Journal / source
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Volume
12
Issue
10
Pages
eadw0891–eadw0891
Publication date
6 March 2026
Language
EN