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Identification and Characterization of Protein Glycosylation using Specific Endo- and Exoglycosidases
Published on: December 26, 2011
Synthesis and Assembly of a New-generation Bifunctional Lipid Nanoparticle for Selective Delivery of mRNA to Antigen
Yi-Fang Zeng1, Tzu-Hao Tseng1, Ruofan Li1,2
1Genomics Research Center, Academia Sinica, 128 Academia Road, Sec 2, Taipei 115, Taiwan.
Abstract:
Described here is the synthesis and assembly of a new-generation mRNA-bifunctional lipid nanoparticle (mRNA-BLNP3) for selective delivery of mRNA to antigen-presenting cells (APCs). Compared to mRNA-BLNP1 and BLNP2 (BioRxiv,doi.org/10.1101/2023.12.26.572282), the mRNA-BLNP3, incorporating a glycolipid with the lipid moiety designed to target the CD1d receptor on dendritic cells (DCs) and the sugar head group targeting the mannose-binding receptors on APCs is more selective with stronger target-specific immune responses. It was shown that vaccination in mice with mRNA-BLNP1 elicited enhanced cytokine induction and antibody responses compared to traditional mRNA-LNPs, and the mRNA-BLNP2 vaccine, incorporating a mannose-glycolipid, further improved DC targeting. However, BLNP3, incorporating the glycolipid with an aryl-mannose head group targeting the mannose receptor on APCs and the same lipid moiety targeting the Cd1d receptor on DCs, showed superior lymph node targeting in vivo with reduced liver accumulation, enhanced mRNA expression in DCs and macrophages, and increased DC maturation. Immunization in mice with mRNA-BLNP3 elicited enhanced humoral and cellular immune responses compared to mRNA-BLNP1 and mRNA-BLNP2, with higher antigen-specific IgG titers and granzyme B-producing CD8+ T cells, demonstrating that BLNP3 is a promising bifunctional lipid nanoparticle for delivery of mRNA vaccines with improved efficacy and safety.
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