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Protamine-Based Strategies for RNA Transfection

Department of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Raemistrasse 100, 8091 Zürich, Switzerland
Faculty of Science, University of Zürich, 8091 Zürich, Switzerland
Faculty of Medicine, University of Zürich, 8091 Zürich, Switzerland
Author to whom correspondence should be addressed.
Academic Editor: Satoshi Uchida
Pharmaceutics 2021, 13(6), 877;
Received: 23 April 2021 / Revised: 28 May 2021 / Accepted: 3 June 2021 / Published: 14 June 2021
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. View Full-Text
Keywords: RNA; protamine; transfection; cancer therapy; vaccines RNA; protamine; transfection; cancer therapy; vaccines
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MDPI and ACS Style

Jarzebska, N.T.; Mellett, M.; Frei, J.; Kündig, T.M.; Pascolo, S. Protamine-Based Strategies for RNA Transfection. Pharmaceutics 2021, 13, 877.

AMA Style

Jarzebska NT, Mellett M, Frei J, Kündig TM, Pascolo S. Protamine-Based Strategies for RNA Transfection. Pharmaceutics. 2021; 13(6):877.

Chicago/Turabian Style

Jarzebska, Natalia T., Mark Mellett, Julia Frei, Thomas M. Kündig, and Steve Pascolo. 2021. "Protamine-Based Strategies for RNA Transfection" Pharmaceutics 13, no. 6: 877.

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