ArticleInternational journal of molecular sciences2026
Genetic Code Expansion Enables Oriented, Site-Specific Conjugation of DARPins to Lipid Nanoparticles for Selective mRNA Delivery to CD8
Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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12 authors.
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Abstract
Lipid nanoparticles (LNPs) are an effective platform for delivering therapeutic payloads, but their use for targeting specific cell populations in vivo is limited by a lack of specificity. To address this issue, we developed an innovative approach for creating targeted LNPs based on the post-insertion of protein-lipid conjugates. By expanding the genetic code, a single p-azido-L-phenylalanine residue was specifically incorporated into a DARPin against murine CD8, enabling copper-free click-chemistry with dibenzocyclooctyne (DBCO) to functionalize the particle surface with DARPin conjugates. DARPin-LNP characterization demonstrated preservation of particle size and acquisition of a characteristic negative charge after DARPin insertion, confirming successful post-insertion. In vitro experiments using primary murine splenic T-cells showed that targeted LNPs selectively transfected CD8
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