Blood advancesMar 13, 2026

Reducing Blood Vessel Leakiness Using Targeted Delivery of VE-Cadherin mRNA

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Anti-CD31 targeted VE-cadherin mRNA LNPs reduced vascular leakage in mouse models of lung edema and ischemic stroke.

Evidence

This was a preclinical mRNA-delivery study in multiple mouse vascular hyperpermeability models, where a single aCD31/tLNP-VEc dose reduced fluid extravasation and macrophage infiltration in bleomycin lung edema and cut post-stroke brain plasma protein leakage by 50%.

Caveat

The study is limited to mouse models and acute permeability endpoints, so human benefit, dosing window, and safety were not tested.

Simplified

Blood vessel hyperpermeability underlies a wide spectrum of potentially fatal diseases ranging from acute pulmonary edema to brain injuries such as ischemic stroke. Yet, effective strategies for rapid rehabilitation of the vascular endothelium to restore vascular homeostasis remain lacking. Here we developed an mRNA therapeutic encoding the vascular membrane structural protein VE-Cadherin (VEc), delivered via an anti-CD31 targeted lipid nanoparticle (aCD31/tLNP-VEc) directly to CD31+ vascular endothelial cells, for the quick restoration of vascular integrity. We showed that administration of a single dose of aCD31/tLNP-VEc significantly ameliorates pathological onsets in multiple mouse models of vascular hyperpermeability. In a bleomycin-induced lung edema model, we found aCD31/tLNP-VEc treatment significantly reduced fluid extravasation and decreased macrophage infiltrations. In a transient middle cerebral artery occlusion (tMCAO)-induced ischemic stroke model, aCD31/tLNP-VEc delivered post-injury diminished plasma protein leakage from brain edema by 50%. Targeted LNP-mediated delivery of VEc mRNA to the vascular network presents a promising platform for treating clinically relevant conditions involving vascular disruption.