The Science

In 2014, the ground breaking discovery of vascular specific LNPs was published in Nature by the pioneers of RNAi/LNP technology, profs Bob Langer and Dan Anderson from MIT. Their unique LNP platform was able to specifically transfect vasculature (vascular endothelium) following a simple iv bolus without expression in the liver (hepatocytes; Dahlman et al, Nature Nanotechnology, 2014).

VasoRx was able to innovative this breakthrough lipoprotein nanoparticle platform which allows targeting of the vasculature: healthy as well as diseased vasculature. The platform is able to transduce with equal efficacy the endothelial lining of large vessels, as well as microvasculature (arterioles and capillaries). The technology has been applied to wide spectrum of disease varying from cardiovascular disease, inflammatory disease, auto immune disease as well as oncology to name a few.

Dysfunctional endothelial cells of the vascular lining contribute to more disease than any other tissue in the body. MicroRNAs (miRNAs) and small interfering RNAs (siRNAs) have the potential to help study and treat endothelial cells by durably silencing multiple genes simultaneously, but efficient RNA delivery has so far remained challenging. Our unique VasoRx polymeric nanoparticles made of low molecular weight polyamines and lipids can deliver RNAi and mRNAs to endothelial cells with extreme high efficiency, thereby facilitating the simultaneous modification of expression of multiple endothelial genes in vivo.

Based on research at Yale University and MIT, endothelial-to-mesenchymal transition has been shown to be a biological process that underlies multiple disease and is responsible for the ongoing chronic vascular inflammation, fibrosis formation, and adaptive (vascular) remodeling, leading to further deterioration of disease process and progressive symptoms.

By blocking the endothelial-to-mesenchymal cell transition in the vascular lining (of endothelial cells), VasoRx has been able, for the first time, to reverse the vascular changes and symptoms seen in cardiovascular and cardiopulmonary disease models, like pulmonary hypertension and atherosclerosis disease models.

By a simple iv infusion of the unique polymeric LNP carrying a specific RNAi for 4 weeks, the vascular changes and elevated pressure in pulmonary vascular bed were significantly alleviated, if not normalized in a pulmonary hypertension disease model.

Likewise, in a high-fat atherosclerosis disease model, treatment with the polymeric LNP carrying a specific RNAi for 4 to 8 weeks, the total volume of pre-existing atherosclerotic plaques was significantly reduced by 60%, with a marked reduction of local inflammatory cells (foam cells) and volume of the necrotic core (so-called, converting a fatty or vulnerable atherosclerotic plaques, into a stable atherosclerotic plaque).  

The unique LNP-RNAi approach safely promotes

Selective silencing of the targeted mRNA in endothelial cells, whereas non-endothelial cells were unaffected for the period of weeks

Reversal of vascular remodeling as seen in pulmonary hypertension and atherosclerosis models

Reversal of the increased pulmonary hypertension in pulmonary hypertension models

Reversal of chronic vascular inflammation (reduction of foam cells and inflammatory cells)

Reversal of vulnerable plaque phenotype into stable fibrotic atherosclerotic plaque