IDMME and IDMDE: inducible CRISPR-dCasRx platforms for spatiotemporal RNA m5C editing

  • Genome Biol. 2026 Jun 12. doi: 10.1186/s13059-026-04150-7.
Jinming Xu  #  1 ,  Jiaju Xu  #  1 ,  Congcong Cao  #  2 ,  Yichang Shu  1 ,  Letian Shen  1 ,  Xuhong He  1 ,  Qi Huangfu  1 ,  Chengfang Sun  1 ,  Weikai Wang  1 ,  Jingchao Wei  1 ,  Ming Cai  1 ,  Bohan Wang  1 ,  Aolin Li  3 ,  Yuchen Liu  4 ,  Jiaming Wen  5
Affiliations
  • 1. Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China.
  • 2. Guangdong Provincial Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Department of Urology, Shenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Synthetic Biology Research Center, Health Science Center, Shenzhen University, Shenzhen, 518035, China.
  • 3. Department of Urology, Shenzhen Second People's Hospital/First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China. [email protected].
  • 4. Guangdong Provincial Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Department of Urology, Shenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Synthetic Biology Research Center, Health Science Center, Shenzhen University, Shenzhen, 518035, China. [email protected].
  • 5. Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China. [email protected].
  • # Contributed equally.
PMID: 42286694 DOI: 10.1186/s13059-026-04150-7
Abstract

RNA 5-methylcytosine (m5C) is a dynamic epigenetic MARK implicated in tumorigenesis, however, existing editors lack spatiotemporal regulation and reversibility. Here, we develop Abscisic acid (ABA)-inducible CRISPR-dCasRx systems for programmable m5C methylation (IDMME) and demethylation (IDMDE). These editors enable site-specific, low off-target m5C modification through ligand-dependent assembly of split effector domains. We further integrate photocaged ABA to achieve light-controlled activation. Application in renal carcinoma models shows that targeted m5C editing modulates transcript function and suppresses tumor growth in vitro and in vivo. This platform provides a versatile, spatiotemporally controllable approach for dissecting RNA epigenetic mechanisms and advancing RNA-based therapeutic strategies.

Keywords
CRISPR dCasRx; Chemical inducible proximity; Epigenetic therapy; RNA m5C methylation; Renal cell carcinoma.
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