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Genetic Code Expansion Enables Oriented, Site-Specific Conjugation of DARPins to Lipid Nanoparticles for Selective mRNA Delivery to CD8+ T Cells.

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Τίτλος: Genetic Code Expansion Enables Oriented, Site-Specific Conjugation of DARPins to Lipid Nanoparticles for Selective mRNA Delivery to CD8+ T Cells.
Συγγραφείς: Dakhnevich A; Biotechnology Department, Sirius University of Science and Technology, 354349 Sirius, Russia., Pateev I; Biotechnology Department, Sirius University of Science and Technology, 354349 Sirius, Russia., Skvortsov IA; Biotechnology Department, Sirius University of Science and Technology, 354349 Sirius, Russia., Yarmachkova S; Biotechnology Department, Sirius University of Science and Technology, 354349 Sirius, Russia., Shevyrev D; Biotechnology Department, Sirius University of Science and Technology, 354349 Sirius, Russia., Chubarova A; Biotechnology Department, Sirius University of Science and Technology, 354349 Sirius, Russia., Gasina M; Biotechnology Department, Sirius University of Science and Technology, 354349 Sirius, Russia., Cherepanova N; Medicinal Chemistry Core Facility, Sirius University of Science and Technology, 354349 Sirius, Russia., Siaglova ED; Biomaterials Core Facility, Sirius University of Science and Technology, 354349 Sirius, Russia., Reshetnikov V; Biotechnology Department, Sirius University of Science and Technology, 354349 Sirius, Russia., Baranov MV; Biotechnology Department, Sirius University of Science and Technology, 354349 Sirius, Russia., Ivanov RA; Biotechnology Department, Sirius University of Science and Technology, 354349 Sirius, Russia.
Πηγή: International journal of molecular sciences [Int J Mol Sci] 2026 Aug 29; Vol. 27 (17). Date of Electronic Publication: 2026 Aug 29.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
Imprint Name(s): Original Publication: Basel, Switzerland : MDPI, [2000-
Ιατρικοί όροι (MeSH): Nanoparticles*/chemistry , CD8-Positive T-Lymphocytes*/metabolism , RNA, Messenger*/genetics , RNA, Messenger*/administration & dosage , RNA, Messenger*/chemistry , Lipids*/chemistry , Genetic Code*, Phenylalanine/chemistry ; Animals ; Mice ; Click Chemistry ; Liposomes
Περίληψη: 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+ T-lymphocytes. These data indicate that the developed platform enables selective in vitro delivery of nucleic acids to cytotoxic lymphocytes, highlighting its potential relevance for designing safer immunotherapeutic strategies.
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Grant Information: 18-03 Scientific and technological development of the «Sirius» Federal Territory
Contributed Indexing: Keywords: CD8 T-cells; DARPin; cell-targeted gene therapy; click-chemistry; genetic code expansion; lipid nanoparticles (LNP); mRNA
Substance Nomenclature: 0 (RNA, Messenger)
0 (Lipid Nanoparticles)
0 (Lipids)
47E5O17Y3R (Phenylalanine)
0 (Liposomes)
Entry Date(s): Date Created: 20260915 Date Completed: 20260915 Latest Revision: 20260916
Update Code: 20260916
PubMed Central ID: PMC13565844
DOI: 10.3390/ijms27177755
PMID: 42737652
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1422-0067
DOI:10.3390/ijms27177755