Enhanced epigenetic modulation via mRNA-encapsulated lipid nanoparticles enables targeted anti-inflammatory control.

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.