Protamine sulfate 50mg/5ml solution for injection ampoules

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.

Abstract licence: CC BY

Male fertility throughout life hinges on the successful production of motile sperm, a developmental process that involves three coordinated transitions: mitosis, meiosis, and spermiogenesis. Germ cells undergo both mitosis and meiosis to generate haploid round spermatids, in which histones bound to the male genome are replaced with small nuclear proteins known as protamines. During this transformation, the chromatin undergoes extensive remodeling to become highly compacted in the sperm head. Despite its central role in spermiogenesis and fertility, we lack a comprehensive understanding of the molecular mechanisms underlying the remodeling process, including which remodelers/chaperones are involved, and whether intermediate chromatin proteins function as discrete steps, or unite simultaneously to drive successful exchange. Furthermore, it remains largely unknown whether more nuanced interactions instructed by protamine post-translational modifications affect chromatin dynamics or gene expression in the early embryo. Here, we bring together past and more recent work to explore these topics and suggest future studies that will elevate our understanding of the molecular basis of the histone-to-protamine exchange and the underlying etiology of idiopathic male infertility.

Abstract licence: CC BY

Macromolecular biomolecules are currently dethroning classical small molecule therapeutics because of their improved targeting and delivery properties. Protamine-a small polycationic peptide-represents a promising candidate. In nature, it binds and protects DNA against degradation during spermatogenesis due to electrostatic interactions between the negatively charged DNA-phosphate backbone and the positively charged protamine. Researchers are mimicking this technique to develop innovative nanopharmaceutical drug delivery systems, incorporating protamine as a carrier for biologically active components such as DNA or RNA. The first part of this review highlights ongoing investigations in the field of protamine-associated nanotechnology, discussing the self-assembling manufacturing process and nanoparticle engineering. Immune-modulating properties of protamine are those that lead to the second key part, which is protamine in novel vaccine technologies. Protamine-based RNA delivery systems in vaccines (some belong to the new class of mRNA-vaccines) against infectious disease and their use in cancer treatment are reviewed, and we provide an update on the current state of latest developments with protamine as pharmaceutical excipient for vaccines.

Abstract licence: CC BY