Nature nanotechnologyJan 19, 2026

Delivering messenger RNA nanoparticles to the uterine lining over time to treat reproductive disorders

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

Ligand-targeted mRNA lipid nanoparticles improved local endometrial protein delivery and embryo implantation in a mouse injury model.

Evidence

This formulation and preclinical mouse study tested ligand-conjugated GM-CSF mRNA-loaded LNPs after intrauterine infusion, measuring endometrial expression, systemic exposure, and implantation rates.

Caveat

The fertility benefit was shown in a murine endometrial injury model, so human safety, dosing, targeting, and pregnancy outcomes remain untested.

Simplified

Dysfunctions of the endometrium, the uterus inner lining, can impair embryo implantation and reduce pregnancy rates. Intrauterine administration of cytokines has shown potential to improve endometrium function, but it is challenged by poor targeting and dose-limiting systemic side effects. Here we present a strategy for introducing therapeutic messenger RNA into the endometrium for the treatment of reproductive disorders. mRNA was loaded into a ligand-conjugated lipid nanoparticle (LNP), enabling multivalent interactions with the temporally overexpressed integrin receptors on the endometrial surface during the window of implantation. Conjugating the targeting ligand directly to the lipid component enhanced endometrial protein expression after intrauterine infusion and reduced systemic expression in the liver and spleen. A single infusion of granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA-loaded LNP sustained local protein expression for several hours and reduced GM-CSF systemic exposure. In a murine model of endometrial injury, GM-CSF mRNA-loaded LNP improved embryo implantation rates, outperforming recombinant GM-CSF. Our strategy demonstrates the efficacy of using mRNA to improve fertility outcomes.

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Delivering messenger RNA nanoparticles to the uterine lining over time to treat reproductive disorders

Abstract

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