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Targeted mRNA Nanomedicine for ARDS and Ventilator-Induced Lung Injury

Lead Inventor: Yun Fang

SUMMARY

A targeted nanomedicine platform improves acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI) outcomes by selectively delivering therapeutic mRNA to inflamed pulmonary microvascular endothelial cells, thereby restoring endothelial function and reducing lung damage.

The Unmet Need: Effective treatments for endothelial dysfunction in ARDS and ventilator-induced lung injury remain limited

  • ARDS and VILI are characterized by severe endothelial dysfunction leading to increased vascular inflammation, impaired barrier integrity, pulmonary edema, and ultimately respiratory failure; current therapeutics do not adequately address the underlying endothelial injury or restore vascular health, contributing to persistent high morbidity and mortality rates.

  • The rapid growth of mRNA therapeutics and targeted nanoparticle delivery technologies offers new opportunities to precisely modulate gene expression in diseased tissues, particularly for conditions involving localized endothelial inflammation such as ARDS and VILI.

The Proposed Solution: VCAM1-targeted liposomal nanoparticles encapsulating therapeutic mRNA to restore endothelial KLF2 expression

  • The faculty inventor developed a platform utilizing liposomal nanoparticles decorated with a peptide targeting VCAM1, an adhesion molecule elevated on inflamed pulmonary microvascular endothelial cells, to selectively deliver functional mRNA encoding Kruppel-like factor 2 (KLF2)
  • This approach restores endothelial barrier function and reduces inflammation in lung injury models. Unlike non-targeted nanoparticle systems, this solution achieves precise mRNA delivery specifically to diseased lung endothelium, addressing the instability and delivery challenges inherent to mRNA therapy. Preclinical validation demonstrated significant reduction of ARDS severity in influenza-infected mice following administration of targeted KLF2-mRNA liposomes, with effects achieved through two intravenous injections.

ADVANTAGES

  • Targeted delivery to inflamed pulmonary endothelium

  • Restoration of endothelial barrier integrity

  • Encapsulation of unstable therapeutic mRNA

  • Reduced pulmonary vascular inflammation

  • Minimization of off-target distribution

  • Demonstrated efficacy in relevant preclinical models

APPLICATIONS

  • Treatment of acute respiratory distress syndrome (ARDS)

  • Prevention and mitigation of ventilator-induced lung injury (VILI)

  • Therapeutic intervention in viral pneumonia-associated lung injury (e.g., influenza H1N1, SARS-CoV-2)