Intranasal oxytocin mRNA-LNP can promote social behaviour and reduce pain

2026 · doi:10.64898/2026.03.18.711938
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The paper studied whether intranasal delivery of mRNA encapsulated in lipid nanoparticles (mRNA-LNP) can achieve functional mRNA expression in the central nervous system and produce therapeutic effects. Using intranasal administration, the authors reported localized mRNA uptake and functional expression in respiratory and olfactory epithelium, with the encoded secreted oxytocin peptide entering the CNS. They found that intranasal mRNA-LNP encoding a synthetic oxytocin transcript enhanced social behaviour and reduced pain responses across multiple behavioural paradigms without impairing motor coordination, and that repeated dosing was well tolerated with no inflammatory response or overall health changes. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract The COVID-19 epidemic and success of mRNA-LNP vaccines demonstrated the transformative potential of mRNA therapeutics. Beyond vaccination, mRNA delivery offers a platform for transient on-demand expression of therapeutic proteins for both rare and common diseases. While delivery of therapeutics to the liver is relatively straightforward, targeted delivery of mRNA-LNPs to the central nervous system (CNS) remains a significant challenge. Here we show that intranasal mRNA-LNP delivery results in localized mRNA cargo uptake and functional expression in the respiratory and olfactory epithelium, where the encoded cargo protein is secreted and can enter the CNS. Guided by genomic data of pain-associated gene expression, we identified secreted proteins as candidate mRNA-encoded analgesics. Intranasal mRNA-LNP encoding a synthetic oxytocin transcript (OXT) resulted in bioactive oxytocin peptide delivery to the CNS. Functionally, intranasal OXT mRNA-LNP enhanced social behaviour and attenuated pain responses across multiple behavioural paradigms, without impairing motor coordination. Importantly, repeated dosing was well tolerated and intranasal mRNA-LNP did not elicit an inflammatory response or alter overall health. Together, these findings establish intranasal mRNA-LNP delivery of secreted ligands as a safe, non-invasive route to target the CNS, unlocking a new class of mRNA therapeutics for pain or other disorders of the brain. One sentence summary Intranasal administration of mRNA-LNP enables local transfection in nasal epithelium and subsequent secretion of therapeutic oxytocin peptides into the brain, promoting social interactions and reducing pain. Competing Interest Statement LL, KF, and GGN are inventors on a provisional patent application related to this work (P0077678AU). LL and GGN are co-founders of Enhanced Analgesics, a company developing technology described in this manuscript. The remaining authors declare no competing interests.

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last seen: 2026-05-20T01:45:00.602351+00:00