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

Year: 2026

Type: article

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.

Source: ACS Synthetic Biology

DOI: 10.1021/acssynbio.5c00188

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

Institutions: University of Pittsburgh, Tsinghua University, University of Toronto, Carnegie Mellon University

Language: English

Topic: RNA Interference and Gene Delivery

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,500

Funders: Cystic Fibrosis Foundation, University of Pennsylvania, University of Pittsburgh, National Institutes of Health, Perelman School of Medicine, University of Pennsylvania, National Institute of Biomedical Imaging and Bioengineering, Eunice Kennedy Shriver National Institute of Child Health and Human Development

Awards: CRISPR logic circuits for safer and controllable gene therapies, Fate, Function and Genetic Engineering of Breast Milk Cells for Infant Therapy

OpenAlex ID: W7124272150

FWCI: 6.143

Cites: 57

Cited by: 10

Related to: 10