2. Academic Validation
  3. Spatiotemporal targeting of messenger RNA lipid nanoparticles to the endometrium for the treatment of reproductive disorders

Spatiotemporal targeting of messenger RNA lipid nanoparticles to the endometrium for the treatment of reproductive disorders

  • Nat Nanotechnol. 2026 Jan 19. doi: 10.1038/s41565-025-02108-7.
Saed Abbasi 1 2,  Jairo Ortiz 3 4,  Kimberly Bockley 3 5,  Hongyu Feng 3 6,  Emily Chen 3 6,  Jordan Miller 3 5,  Marina Better 3 5,  Charles Eberhart 7,  Neomi Jerry 3 8,  Justin Hanes 3 4 5 6 9,  James H Segars 10,  Laura M Ensign 11 12 13 14 15 16
Affiliations

Affiliations

  • 1 Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. [email protected].
  • 2 Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. [email protected].
  • 3 Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • 4 Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • 5 Department of Physiology, Pharmacology and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • 6 Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
  • 7 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • 8 Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD, USA.
  • 9 Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
  • 10 Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • 11 Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. [email protected].
  • 12 Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. [email protected].
  • 13 Department of Physiology, Pharmacology and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. [email protected].
  • 14 Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA. [email protected].
  • 15 Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA. [email protected].
  • 16 Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. [email protected].
PMID: 41555025 DOI: 10.1038/s41565-025-02108-7
Abstract

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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