期刊
PHARMACEUTICS
卷 13, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics13060877
关键词
RNA; protamine; transfection; cancer therapy; vaccines
资金
- University of Zurich (URPP Translational Cancer Research)
- department of Dermatology at the University Hospital of Zurich
- Stiftung fur wissenschaftliche Forschung an der Universitat Zurich
- Swiss National Science Found NRP 78 program [4078PO_198321]
- EU [965135]
Protamine is a natural cationic peptide mixture used for heparin neutralization and slow-release insulin formulations. It is also employed for cellular delivery of nucleic acids. Protamine plays a dual role in RNA stabilization, protecting against degradation and enhancing cell penetration.
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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