Boosting ribosomal translation <i>via</i> ionizable lipid-hydrogel microplexes for localized mRNA therapy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41567985.
- Also identified by DOI 10.1016/j.bioactmat.2026.01.007 and PMC identifier 12818249.
- Licence recorded as CC BY-NC-ND.
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Abstract
mRNA therapy holds immense promise for regenerative medicine; however, localized endoplasmic reticulum stress (ERS) in damaged tissues can impair the critical process of ribosomal translation. Here, we developed an <i>in situ</i> injectable lipid nanoparticle (LNP)/microsphere complex, also referred to as a lipid-hydrogel microplex (iLMP), with ERS-alleviating functionality to increase ribosomal translation. A vitamin E-derived ionizable lipid was synthesized to replace conventional ionizable lipids in LNPs, whereas porous hydrogel microspheres stabilized the LNPs <i>via</i> physical adsorption. <i>In vitro</i> studies revealed that the iLMPs codelivered vitamin E and mRNA, mitigating ERS and reducing eIF2α phosphorylation, a key translational barrier. Additionally, iLMPs injected <i>in situ</i> rapidly reconstructed the extracellular matrix, promoting tissue repair. In a bone defect animal model, iLMPs significantly enhanced BMP-2 mRNA translation, promoting osteogenesis. In summary, we present a novel <i>in situ</i> injectable mRNA delivery platform that enhances ribosomal translation, offering a promising strategy for tissue regeneration.