Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Protamine for RNA Transfection: From Heparin Antagonist to RNA Delivery

Version 1 : Received: 23 April 2021 / Approved: 26 April 2021 / Online: 26 April 2021 (13:37:51 CEST)

A peer-reviewed article of this Preprint also exists.

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

Journal reference: Pharmaceutics 2021, 13, 877
DOI: 10.3390/pharmaceutics13060877

Abstract

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 marks60 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.

Keywords

RNA; Protamine; Transfection; Cancer Therapy; Vaccines

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