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Review
. 2025 May;103(5):511-529.
doi: 10.1007/s00109-025-02533-0. Epub 2025 Mar 25.

DNA-RNA hybrids in inflammation: sources, immune response, and therapeutic implications

Litao Chen #  1 , Lechen Hu #  1 , Han Chang #  1 , Jianing Mao #  1 , Meng Ye  2 , Xiaofeng Jin  3
Affiliations
Review

DNA-RNA hybrids in inflammation: sources, immune response, and therapeutic implications

Litao Chen et al. J Mol Med (Berl). 2025 May.

Abstract

Cytoplasmic DNA-RNA hybrids are emerging as important immunogenic nucleic acids, that were previously underappreciated. DNA-RNA hybrids, formed during cellular processes like transcription and replication, or by exogenous pathogens, are recognized by pattern recognition receptors (PRRs), including cGAS, DDX41, and TLR9, which trigger immune responses. Post-translational modifications (PTMs) including ubiquitination, phosphorylation, acetylation, and palmitoylation regulate the activity of PRRs and downstream signaling molecules, fine-tuning the immune response. Targeting enzymes involved in DNA-RNA hybrid metabolism and PTMs regulation offers therapeutic potential for inflammatory diseases. Herein, we discuss the sources, immune response, and therapeutic implications of DNA-RNA hybrids in inflammation, highlighting the significance of DNA-RNA hybrids as potential targets for the treatment of inflammation.

Keywords: DNA-RNA hybrids; Immune response; Inflammatory therapy; PTMs regulation; cGAS-STING pathway.

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Conflict of interest statement

Declarations. Ethics approval: Unethical issues (including plagiarism, informed consent, misconduct, data fabrication, forgery, duplication and/or submission, and redundancy) have been investigated by the authors. Consent for publication: All authors consent for this submission. Competing interests: The authors declare no competing interests.

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