Endothelium-Targeted mRNA Therapeutics For Acute And Chronic Vascular Disease

SUMMARY

Targeted delivery of therapeutic mRNA to inflamed vascular endothelial cells, achieving localized reduction of vascular inflammation and arterial plaque formation to improve treatment outcomes in arterial diseases by using VCAM1-directed liposome nanoparticles.

The Unmet Need: Targeted treatment of localized vascular inflammation in arterial diseases

• Arterial diseases such as atherosclerosis, ischemic stroke, and stenosis develop predominantly at localized vascular sites subject to disturbed blood flow, which current systemic therapies do not adequately address; existing mRNA therapeutics face challenges including instability, poor tissue specificity, and off-target effects limiting their clinical utility for these vascular conditions.

• Advancements in nanomedicine and mRNA technology, combined with a deeper understanding of vascular biology and human genetics, have created an opportunity to develop platforms capable of site-specific delivery of therapeutics to diseased endothelium, thereby overcoming systemic toxicity and enhancing treatment precision.

The Proposed Solution: VCAM1-targeting lipid nanoparticle platform for selective mRNA delivery to inflamed endothelium

• The faculty inventor developed a liposome nanoparticle system engineered to encapsulate functional mRNA and display targeting peptides specific for vascular cell adhesion molecule 1 (VCAM1), which is upregulated on inflamed endothelial cells; this enables intravenous administration that preferentially delivers therapeutic mRNAs, such as phospholipid phosphatase 3 (PLPP3) or Kruppel-like factor 2 (KLF2), to inflamed vascular sites.

• This approach distinguishes itself from existing nanoparticle systems by combining tissue-specific targeting with functional gene replacement informed by human genetics, as demonstrated in multiple preclinical mouse models showing substantial reductions in vascular inflammation, plaque burden, and lung injury without systemic off-target effects or toxicity. The platform is adaptable to various lipid formulations and targeting ligands, supporting both acute and chronic vascular disease interventions.

ADVANTAGES

• Precise targeting of inflamed vascular endothelium

• Encapsulation of functional therapeutic mRNA

• Reduced systemic inflammatory side effects

• Modular nanoparticle design adaptable to diverse targets

• Prolonged mRNA circulation and enhanced cellular uptake

• Validated efficacy in multiple preclinical disease models

APPLICATIONS

• Atherosclerosis and arterial stenosis

• Management of ischemic stroke by vascular inflammation reduction