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Carriers for RNA delivery must be dynamic, first stabilizing and protecting therapeutic RNA during delivery to the target tissue and across cellular membrane barriers and then releasing the cargo in bioactive form. The chemical space of carriers ranges from small cationic lipids applied in lipoplexes and lipid nanoparticles, over medium-sized sequence-defined xenopeptides, to macromolecular polycations applied in polyplexes and polymer micelles. This perspective highlights the discovery of distinct virus-inspired dynamic processes that capitalize on mutual nanoparticle-host interactions to achieve potent RNA delivery. From the host side, subtle alterations of pH, ion concentration, redox potential, presence of specific proteins, receptors, or enzymes are cues, which must be recognized by the RNA nanocarrier via dynamic chemical designs including cleavable bonds, alterable physicochemical properties, and supramolecular assembly-disassembly processes to respond to changing biological microenvironment during delivery.

Competing Interests: Competing interests statement:The authors declare no competing interest.

Titel:	Dynamic carriers for therapeutic RNA delivery.
Autor/in / Beteiligte Person:	Berger, S ; Lächelt, U ; Wagner, E
Zeitschrift:	Proceedings of the National Academy of Sciences of the United States of America, Jg. 121 (2024-03-12), Heft 11, S. e2307799120
Veröffentlichung:	Washington, DC : National Academy of Sciences, 2024
Medientyp:	academicJournal
ISSN:	1091-6490 (electronic)
DOI:	10.1073/pnas.2307799120
Schlagwort:	Cell Membrane Polymers RNA Cues Micelles
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Proc Natl Acad Sci U S A] 2024 Mar 12; Vol. 121 (11), pp. e2307799120. <i>Date of Electronic Publication: </i>2024 Mar 04. MeSH Terms: Cues* ; Micelles* ; Cell Membrane ; Polymers ; RNA References: Adv Sci (Weinh). 2023 Jul;10(19):e2301929. (PMID: 37092557) ; J Control Release. 2023 May;357:394-403. (PMID: 37028451) ; Mol Ther. 2017 Jul 5;25(7):1476-1490. (PMID: 28274797) ; Adv Mater. 2020 Mar;32(12):e1906128. (PMID: 31999380) ; ChemMedChem. 2014 Sep;9(9):2104-10. (PMID: 24504614) ; Chem Rev. 2015 Oct 14;115(19):11043-78. (PMID: 25872804) ; J Bacteriol. 1962 Nov;84:1035-40. (PMID: 13989646) ; Adv Mater. 2019 Oct;31(41):e1902251. (PMID: 31465135) ; Mol Ther. 2009 May;17(5):872-9. (PMID: 19259063) ; J Am Chem Soc. 2023 Jul 19;145(28):15171-15179. (PMID: 37395536) ; Mol Pharm. 2009 May-Jun;6(3):752-62. (PMID: 19348503) ; Biomaterials. 2016 Mar;82:221-8. 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Dynamic carriers for therapeutic RNA delivery.