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April 12, 2026Chinese Science Bulletin (Chinese Version)0 citationsOpen Access

Engineered Vesicular System Modulates m6A-Dependent RNA Stability for Precision Gene Therapy of Malignant Tumors

YLYan LiBLBingjie LuoSCSuifang Chen

Key Points

  • The research aims to develop a targeted delivery system to enhance m6A-dependent RNA stability for treating malignant tumors.
  • Engineered exosomes were created to deliver METTL3.
  • Folic acid was used to enhance specificity for triple negative breast cancer (TNBC) cells.
  • The efficacy of the system was evaluated in vitro and in vivo to assess tumor growth suppression.
  • Overexpression of METTL3 restored m6A-dependent RNA degradation pathways.
  • The engineered exosome system effectively reduced RPL19 mRNA stability.
  • Significant tumor growth inhibition was observed in both in vitro and in vivo experiments.

Abstract

RNA表观遗传修饰是调控基因表达的重要机制, 其中N6-甲基腺苷（N6-methyladenosine, m6A）是最常见且最具研究价值的修饰类型之一. m6A修饰可影响RNA的稳定性、翻译效率及降解过程, 其异常调控已被证实与多种恶性肿瘤的发生发展密切相关. 然而, 受制于递送系统选择性不足及全身毒性风险, 目前实现对RNA甲基化的精准调控仍存在显著挑战. 针对上述问题, 本研究构建了一种工程化细胞外泌体（exosome, Exo）平台, 用于靶向递送m6A甲基转移酶样蛋白3（methyltransferase like 3, METTL3）, 以重编程RNA表观遗传稳态. 通过在外泌体表面修饰叶酸（folic acid, FA）配体, 该系统能够特异识别并富集于三阴性乳腺癌（triple negative breast cancer, TNBC）组织, 实现高效而精准的基因递送. 且在本研究中, METTL3的过表达可有效恢复m6A依赖的RNA降解通路, 并选择性降低RPL19 mRNA的稳定性, 从而在体内外实验中显著抑制肿瘤生长. 该递送系统具有优良的生物相容性、极低的脱靶风险及良好的生物安全性, 突破了传统病毒载体和合成载体的主要局限, 为基于METTL3的TNBC靶向治疗提供了一种具有广阔应用前景的新策略.

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Cite This Study

Li et al. (2026) studied this question.

synapsesocial.com/papers/69db37044fe01fead37c5065https://doi.org/10.1360/csb-2025-5862
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1METTL3-dependent m6A modification in cancer treatment resistance and its therapeutic implications2026
  2. 2A Stapled Peptide Inhibitor Targeting the Binding Interface of N6‐Adenosine‐Methyltransferase Subunits METTL3 and METTL14 for Cancer Therapy2024 · 26 citations
  3. 3A Stapled Peptide Inhibitor Targeting the Binding Interface of N6‐Adenosine‐Methyltransferase Subunits METTL3 and METTL14 for Cancer Therapy2024 · 6 citations
  4. 4Functional and clinical significance of the RNA m6A methyltransferase complex in breast cancer2025
  5. 5HGG-18. Manipulation of the RNA modification m6A to induce tumor-specific antigens in high-grade glioma2025