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 . 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.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888353 | PMC |
http://dx.doi.org/10.1101/2025.02.24.639996 | DOI Listing |
RSC Chem Biol
February 2025
Pingshan Translational Medicine Center, Shenzhen Bay Laboratory Shenzhen 518118 China
mRNA-based therapies have broad applications in various disease treatments and have been applied in protein replacement therapy, gene editing, and vaccine development. Numerous research studies have been carried out aiming to increase the stability of mRNA, improve its translational efficiency, and reduce its immunogenicity. However, given mRNA's large molecular size and strong electronegativity, the safety and efficient delivery of mRNA into the target cells remains the critical rate-limiting step in current mRNA drug development.
View Article and Find Full Text PDFRSC Adv
March 2025
Institute of Pharmaceutical Research, GLA University Mathura India.
Onychomycosis significantly impacts approximately 20% of the global population. The physical barriers of the nail structure make fungal infections a persistent therapeutic challenge. Traditional approaches, including topical and oral antifungal agents, have limitations such as toxicities, low nail permeability, adverse effects, and high recurrence rates.
View Article and Find Full Text PDFCurr Gene Ther
March 2025
Department of Pharmaceutical Sciences, Indira Gandhi University, Meerpur, Rewari - 123401, India.
The advent of CRISPR/Cas gene-editing technology has revolutionized molecular biology, offering unprecedented precision and potential in treating genetic disorders, cancers, and other complex diseases. However, for CRISPR/Cas to be truly effective in clinical settings, one of the most significant challenges lies in the delivery of the CRISPR components, including guide RNA (gRNA) and Cas protein, into specific cells or tissues. Safe, targeted, and efficient delivery remains a critical bottleneck.
View Article and Find Full Text PDFNat Protoc
March 2025
Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
mRNA-based therapies have emerged as a cutting-edge approach for diverse therapeutic applications. However, substantial barriers exist that hinder scientists from entering this research field, including the technical complexity and multiple potential workflows available for formulating and evaluating mRNA lipid nanoparticles (LNPs). Here we present an easy-to-follow and step-by-step guide for mRNA LNP formulation, characterization and in vitro and in vivo evaluation that could lower these barriers, facilitating entry for scientists in academia, industry and clinical settings into this research space.
View Article and Find Full Text PDFJ Am Chem Soc
March 2025
Institute of Medical Science, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
Lipid nanoparticles (LNPs) are widely used for delivering therapeutic nucleic acids, yet the relationship between their internal structure and intracellular behavior, particularly before RNA release, remains unclear. Here, we elucidate how lipid-siRNA organization within LNPs can modulate their intracellular delivery dynamics. We use cryo-electron microscopy and photochemical assays to reveal that increased siRNA loading can reduce helper lipids' distribution to the LNP surface, while siRNA consistently localizes near the surface.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!