Reversible one-step acylation facilitates mitochondrial delivery of functional RNA.

Yuli Zhuang, Xia Liu, Yuxuan Shen, Qiuyue Wang, Zhimin Lin, Qian Zeng, Xin Chen, Linye Jiang, Shao Q Yao, Jingyan Ge

Abstract read

In one paragraph

Article in Chemical science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Yuli ZhuangState Key Laboratory of Green Chemical Synthesis and Conversion, Zhejiang Key Laboratory of Bioorganic Synthesis, College of Biotechnology and Bioengineering, Zhejiang University of Technology Hangzhou 310014 China gejy@zjut.edu.cn.

Xia LiuDepartment of Chemistry, National University of Singapore 117543 Singapore.

Yuxuan ShenState Key Laboratory of Green Chemical Synthesis and Conversion, Zhejiang Key Laboratory of Bioorganic Synthesis, College of Biotechnology and Bioengineering, Zhejiang University of Technology Hangzhou 310014 China gejy@zjut.edu.cn.

Qiuyue WangState Key Laboratory of Green Chemical Synthesis and Conversion, Zhejiang Key Laboratory of Bioorganic Synthesis, College of Biotechnology and Bioengineering, Zhejiang University of Technology Hangzhou 310014 China gejy@zjut.edu.cn.

Zhimin LinState Key Laboratory of Green Chemical Synthesis and Conversion, Zhejiang Key Laboratory of Bioorganic Synthesis, College of Biotechnology and Bioengineering, Zhejiang University of Technology Hangzhou 310014 China gejy@zjut.edu.cn.

Qian ZengState Key Laboratory of Green Chemical Synthesis and Conversion, Zhejiang Key Laboratory of Bioorganic Synthesis, College of Biotechnology and Bioengineering, Zhejiang University of Technology Hangzhou 310014 China gejy@zjut.edu.cn.

Xin ChenState Key Laboratory of Green Chemical Synthesis and Conversion, Zhejiang Key Laboratory of Bioorganic Synthesis, College of Biotechnology and Bioengineering, Zhejiang University of Technology Hangzhou 310014 China gejy@zjut.edu.cn.

Linye JiangState Key Laboratory of Green Chemical Synthesis and Conversion, Zhejiang Key Laboratory of Bioorganic Synthesis, College of Biotechnology and Bioengineering, Zhejiang University of Technology Hangzhou 310014 China gejy@zjut.edu.cn.

Shao Q YaoDepartment of Chemistry, National University of Singapore 117543 Singapore.ORCID https://orcid.org/0000-0003-4715-769X

Jingyan GeState Key Laboratory of Green Chemical Synthesis and Conversion, Zhejiang Key Laboratory of Bioorganic Synthesis, College of Biotechnology and Bioengineering, Zhejiang University of Technology Hangzhou 310014 China gejy@zjut.edu.cn.ORCID https://orcid.org/0000-0003-0139-3355

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mitochondria-targeted RNA therapeutics hold promise for treating mitochondrial disorders and cancer, yet effective mitochondrial gene modulation remains challenging due to the strong negative charge and intrinsic instability of RNA, which hinder transport across the mitochondrial double membrane. Herein, we demonstrate, for the first time, mitochondrial RNA delivery enabled by reversible 2'-hydroxyl (2'-OH) acylation chemistry. Installation of a triphenylphosphonium (TPP)-bearing acyl group at the RNA 2'-OH in a single step creates a plug-and-play platform that simultaneously enhances RNA stability and directs selective mitochondrial accumulation, while allowing spontaneous recovery of native RNA structure and activity. In cell-based assays, this strategy enables efficient and selective silencing of mitochondria-encoded genes with minimal off-target effects. Importantly,

Identifiers

PMID42326347

DOI10.1039/d6sc01497f

PMCPMC13280551

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