Enhanced Epigenetic Modulation via mRNA-Encapsulated Lipid Nanoparticles Enables Targeted Anti-inflammatory Control

ACS Synthetic Biology 2026 Open access

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Authors: Tahere Mokhtari, Mohammad Nasser Taheri, Sarah Akhlaghi, Armin Aryannejad, Yuda Xiang, Vineet Mahajan, Kamyar Keshavarz, Amirreza Kiani, S. Yang, Samuel T. LoPresti, Ryan LeGraw, Kathryn A. Whitehead
+1 more Samira Kiani
DOI: 10.1021/acssynbio.5c00188
Cited by: 2
References: 57

Abstract

High Resolution Image Download MS PowerPoint Slide 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.

Fields of Study & Subjects

RNA Interference and Gene Delivery Immunotherapy and Immune Responses Immune responses and vaccinations

Publication details

Journal / source
ACS Synthetic Biology
Publisher
American Chemical Society (ACS)
Volume
15
Issue
2
Pages
400–410
Publication date
15 January 2026
Language
EN