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**p5RHH:Sod2 mRNA polyplexes** are a research-stage peptide–mRNA nanoparticle therapeutic that complexes murine *Sod2* mRNA with p5RHH, an amphipathic cationic peptide derived from melittin. The self-assembled particles are approximately 50–55 nm in diameter and can be coated with hyaluronic acid to improve post-assembly stability. Following systemic administration in murine models, the construct delivers *Sod2* mRNA to target tissues, increasing expression of mitochondrial superoxide dismutase 2 and reducing mitochondrial oxidative stress. In experimental abdominal aortic aneurysm, treatment mitigated aneurysm expansion and largely prevented rupture; associated effects included reduced inducible nitric oxide synthase expression, platelet activation and aggregation, vascular inflammatory signaling, and MAPK-pathway activity. The same p5RHH-based *Sod2* mRNA nanoparticle approach has also shown plaque-stabilizing activity in murine advanced atherosclerosis models. It has no INN, brand name, known commercial developer, clinical trial program, or approved status. ([thno.org](https://www.thno.org/v15p4016.htm))
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