Protamine-Based Strategies for RNA Transfection

Protamine is a natural cationic peptide mixture mostly known as a drug for the neutralization of heparin and as a compound in formulations of slow-release insulin. Protamine is also used for cellular delivery of nucleic acids due to opposite charge-driven coupling. This year marks 60 years since the...

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Autores principales: Natalia Teresa Jarzebska, Mark Mellett, Julia Frei, Thomas M. Kündig, Steve Pascolo
Formato: Artículo
Lenguaje:English
Publicado: MDPI AG 2021-06-01
Colección:Pharmaceutics
Materias:
Acceso en línea:https://www.mdpi.com/1999-4923/13/6/877
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author Natalia Teresa Jarzebska
Mark Mellett
Julia Frei
Thomas M. Kündig
Steve Pascolo
author_facet Natalia Teresa Jarzebska
Mark Mellett
Julia Frei
Thomas M. Kündig
Steve Pascolo
author_sort Natalia Teresa Jarzebska
collection DOAJ
description Protamine is a natural cationic peptide mixture mostly known as a drug for the neutralization of heparin and as a compound in formulations of slow-release insulin. Protamine is also used for cellular delivery of nucleic acids due to opposite charge-driven coupling. This year marks 60 years since the first use of Protamine as a transfection enhancement agent. Since then, Protamine has been broadly used as a stabilization agent for RNA delivery. It has also been involved in several compositions for RNA-based vaccinations in clinical development. Protamine stabilization of RNA shows double functionality: it not only protects RNA from degradation within biological systems, but also enhances penetration into cells. A Protamine-based RNA delivery system is a flexible and versatile platform that can be adjusted according to therapeutic goals: fused with targeting antibodies for precise delivery, digested into a cell penetrating peptide for better transfection efficiency or not-covalently mixed with functional polymers. This manuscript gives an overview of the strategies employed in protamine-based RNA delivery, including the optimization of the nucleic acid’s stability and translational efficiency, as well as the regulation of its immunostimulatory properties from early studies to recent developments.
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spelling doaj.art-925b8efb3b5e4c179122823142014bf22023-11-22T00:01:48ZengMDPI AGPharmaceutics1999-49232021-06-0113687710.3390/pharmaceutics13060877Protamine-Based Strategies for RNA TransfectionNatalia Teresa Jarzebska0Mark Mellett1Julia Frei2Thomas M. Kündig3Steve Pascolo4Department of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Raemistrasse 100, 8091 Zürich, SwitzerlandDepartment of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Raemistrasse 100, 8091 Zürich, SwitzerlandDepartment of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Raemistrasse 100, 8091 Zürich, SwitzerlandDepartment of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Raemistrasse 100, 8091 Zürich, SwitzerlandDepartment of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Raemistrasse 100, 8091 Zürich, SwitzerlandProtamine is a natural cationic peptide mixture mostly known as a drug for the neutralization of heparin and as a compound in formulations of slow-release insulin. Protamine is also used for cellular delivery of nucleic acids due to opposite charge-driven coupling. This year marks 60 years since the first use of Protamine as a transfection enhancement agent. Since then, Protamine has been broadly used as a stabilization agent for RNA delivery. It has also been involved in several compositions for RNA-based vaccinations in clinical development. Protamine stabilization of RNA shows double functionality: it not only protects RNA from degradation within biological systems, but also enhances penetration into cells. A Protamine-based RNA delivery system is a flexible and versatile platform that can be adjusted according to therapeutic goals: fused with targeting antibodies for precise delivery, digested into a cell penetrating peptide for better transfection efficiency or not-covalently mixed with functional polymers. This manuscript gives an overview of the strategies employed in protamine-based RNA delivery, including the optimization of the nucleic acid’s stability and translational efficiency, as well as the regulation of its immunostimulatory properties from early studies to recent developments.https://www.mdpi.com/1999-4923/13/6/877RNAprotaminetransfectioncancer therapyvaccines
spellingShingle Natalia Teresa Jarzebska
Mark Mellett
Julia Frei
Thomas M. Kündig
Steve Pascolo
Protamine-Based Strategies for RNA Transfection
Pharmaceutics
RNA
protamine
transfection
cancer therapy
vaccines
title Protamine-Based Strategies for RNA Transfection
title_full Protamine-Based Strategies for RNA Transfection
title_fullStr Protamine-Based Strategies for RNA Transfection
title_full_unstemmed Protamine-Based Strategies for RNA Transfection
title_short Protamine-Based Strategies for RNA Transfection
title_sort protamine based strategies for rna transfection
topic RNA
protamine
transfection
cancer therapy
vaccines
url https://www.mdpi.com/1999-4923/13/6/877
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AT thomasmkundig protaminebasedstrategiesforrnatransfection
AT stevepascolo protaminebasedstrategiesforrnatransfection