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 <i>in vivo</i>. 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.
Authors
- Ryan LeGraw (ORCID: https://orcid.org/0000-0002-5742-0706)
- Kathryn A. Whitehead (ORCID: https://orcid.org/0000-0002-0100-7824)
- Vineet Mahajan (ORCID: https://orcid.org/0000-0001-5243-9590)
- Armin Aryannejad (ORCID: https://orcid.org/0000-0002-1354-5566)
- Sarah Akhlaghi
- Tahere Mokhtari (ORCID: https://orcid.org/0009-0009-9015-8314)
- Samira Kiani
- Mohammad Nasser Taheri
- S. Yang
- Amirreza Kiani
- Yuda Xiang (ORCID: https://orcid.org/0000-0002-3812-4944)
- Kamyar Keshavarz
- Samuel LoPresti
Institutions
- University of Pittsburgh (US)
- University of Toronto (CA)
- Bruin Biometrics (United States) (US)
- Genex Systems (United States) (US)
- Carnegie Mellon University (US)
- Tsinghua University (CN)
Publication Details
- Journal
- ACS Synthetic Biology
- Published
- 2026-01-15
- DOI
- https://doi.org/10.1021/acssynbio.5c00188
- Primary Topic
- RNA Interference and Gene Delivery
- Type
- article
- Field-Weighted Citation Impact
- 0.00