# Enhanced Epigenetic Modulation via mRNA-Encapsulated Lipid Nanoparticles Enables Targeted Anti-inflammatory Control **Authors:** Tahere Mokhtari, Mohammad N. Taheri, Sarah Akhlaghi, Armin Aryannejad, Yuda Xiang, Vineet Mahajan, Kamyar Keshavarz, Amirreza Kiani, Samantha Yang, Samuel LoPresti, Ryan LeGraw, Kathryn A. Whitehead, Samira Kiani PMC · DOI: 10.1021/acssynbio.5c00188 · ACS Synthetic Biology · 2026-01-15 ## TL;DR A new method using lipid nanoparticles to control inflammation by targeting immune genes shows promise for treating inflammatory diseases. ## Contribution An enhanced ZF-based repressor delivered via lipid nanoparticles enables targeted immunomodulation. ## Key findings - Targeting Myd88 with lipid nanoparticles reduces inflammation in mice. - The system improves AAV administration by reducing antibody responses. - This approach offers a safe platform for immunomodulation in inflammatory diseases. ## Abstract Temporal transcriptional modulation of immune-related genes offers powerful therapeutic potential for treating inflammatory diseases. Here we introduce an enhanced zinc finger (ZF)-based transcriptional repressor delivered via lipid nanoparticles for controlling immune signaling pathways in vivo. By targeting Myd88, an essential adaptor molecule involved in immunity, our system demonstrates therapeutic efficacy against septicemia in C57BL/6J mice and improves repeated AAV administration by reducing antibody responses. This epigenetic engineering approach provides a platform for safe and efficient immunomodulation applicable across diseases caused by imbalanced inflammatory responses. ## Linked entities - **Genes:** MYD88 (MYD88 innate immune signal transduction adaptor) [NCBI Gene 4615] ## Full-text entities - **Genes:** Myd88 (myeloid differentiation primary response gene 88) [NCBI Gene 17874] - **Diseases:** septicemia (MESH:D018805), inflammatory (MESH:D007249) - **Chemicals:** Lipid (MESH:D008055) - **Species:** Mus musculus (house mouse, species) [taxon 10090] ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12930510/full.md ## Figures 2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12930510/full.md ## References 58 references — full list in the complete paper: https://tomesphere.com/paper/PMC12930510/full.md --- Source: https://tomesphere.com/paper/PMC12930510