Nona-arginine

Summary

Nona-arginine (R9) is a synthetic nine-residue polyarginine peptide widely used in research as a cell-penetrating peptide (CPP) carrier. It is not an approved therapeutic agent but serves as a delivery vehicle for nucleic acids, proteins, imaging agents, and drugs across cellular membranes. R9 has been extensively studied for its superior intracellular delivery efficiency compared to shorter polyarginine sequences.

Mechanism of Action

Nona-arginine (R9) is a polyarginine cell-penetrating peptide that facilitates intracellular delivery of cargo through electrostatic interactions with negatively charged cell membrane components (e.g., heparan sulfate proteoglycans), followed by endocytosis or direct membrane translocation. The guanidinium groups of the nine arginine residues form bidentate hydrogen bonds with membrane phosphates and sulfates, promoting cellular uptake.

Routes of Administration

Goals & Uses

• Transdermal delivery enhancementDrug DeliveryLow
• Intracellular drug deliveryDrug DeliveryHigh
• Vaccine adjuvant / antigen deliveryImmunologyLow
• Imaging agent deliveryDiagnosticsModerate
• Gene therapy vector enhancementGene TherapyModerate

Contraindications

• In vivo systemic use without validated formulationSafetyHigh
• Known hypersensitivity to polyarginine peptidesAllergy/ImmunologyHigh

Adverse Effects

• Cytotoxicity at high concentrationsIn Vitro ToxicityCommon
• Endosomal entrapment / inefficient endosomal escapePharmacokinetic LimitationCommon
• Membrane disruptionCellular ToxicityUncommon
• Complement activation / immunogenicityImmunologicalUnknown

Drug Interactions

• Anionic polymers (e.g., polyglutamic acid, DNA)Moderate
• Heparin / heparan sulfate-based compoundsHigh

Population Constraints

• Pregnant or lactating individualsReproductiveRelative
• Pediatric populationsAgeRelative
• Immunocompromised individualsImmunologicalRelative

Regulatory Status

• European UnionUnapprovedNot authorized by EMA; used only in academic/preclinical research.
• United StatesUnapprovedResearch tool only; no IND or NDA on record for R9 as a standalone therapeutic.
• United KingdomUnapprovedNot approved by MHRA; research use only.

Not approved by FDA, EMA, or any major regulatory agency as a therapeutic. Used exclusively in preclinical and early research settings as a molecular tool or delivery vector. No clinical approvals on record.

Evidence & Sources

No sources recorded yet.