# Development of lesion-targeted lncRNA nanotherapeutic for vascular smooth muscle dysfunction > **NIH NIH R56** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2024 · $407,975 ## Abstract PROJECT SUMMARY Neointimal hyperplasia (NIH) is a significant issue that arises from vascular damage during interventions, leading to arterial wall thickening and lumen loss. This condition is primarily caused by the phenotypic transition of vascular smooth muscle cells (VSMCs). Excessive migration and proliferation of these dysfunctional VSMCs contribute to NIH, which ultimately causes stenosis and restricts blood flow. Preventing or reversing this pathological transition in VSMCs could be a promising strategy to mitigate NIH following interventions. Recent studies have identified a long noncoding RNA called cardiac mesoderm enhancer-associated noncoding RNA (CARMN), which plays a critical role in VSMC differentiation and maintenance of contractile functions. Disruptions in CARMN regulation have been linked to VSMC dysfunction and NIH. Decreased expression of CARMN has been observed in dedifferentiated VSMCs and diseased blood vessels. Furthermore, studies have shown that genetic ablation of CARMN exacerbates neointima formation, while CARMN overexpression attenuates NIH in mouse and rat models of vascular injury. These findings strongly suggest that restoring CARMN regulation in dysfunctional VSMCs could be a viable strategy to mitigate NIH and improve the outcomes of vascular interventions. Based on these insights, our research project aims to develop a lesion- targeted nanotherapeutic that utilizes CARMN transcripts as the pharmaceutical agent for the treatment of VSMC dysfunction and NIH. Building on our prior successful research with platelet membrane-cloaked nanoparticles (PNP) as an efficient targeted delivery system for injured vasculature, we have integrated in vitro transcribed (IVT) CARMN RNA into PNP, creating PNP-CARMN. Our preliminary findings demonstrate that PNP significantly increases the uptake of CARMN by cultured VSMCs and improves targeted delivery of CARMN in the denuded mouse artery. Importantly, in mice subjected to a wire-injury procedure, PNP-CARMN effectively mitigates arterial wall thickening compared to those loaded with GFP mRNA. These preliminary results indicate that PNP-CARMN has the potential to address VSMC dysfunction and prevent NIH. The research project will test the overall hypothesis that CARMN transcripts delivered by PNP would selectively accumulate in the vascular injury sites and promote VSMC contractile gene expression and functions, there mitigating NIH. The proposed studies involve three Specific Aims, including (1) optimize PNP-CARMN for nuclear delivery and assess its in vitro effects, (2) investigate the pharmacokinetics and toxicity of PNP-CARMN, and (3) evaluate the pharmacological responses and therapeutic efficacy of PNP-CARMN against VSMC dysfunction and NIH. Successful completion of these Aims will provide insight into the therapeutic role of CARMN and contribute to the development of a new avenue for CVD treatments that can benefit millions of Americans. ## Key facts - **NIH application ID:** 11192960 - **Project number:** 1R56HL173828-01 - **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS - **Principal Investigator:** Mark Kuei-Chun Wang - **Activity code:** R56 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $407,975 - **Award type:** 1 - **Project period:** 2024-09-24 → 2026-08-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/11192960 ## Citation > US National Institutes of Health, RePORTER application 11192960, Development of lesion-targeted lncRNA nanotherapeutic for vascular smooth muscle dysfunction (1R56HL173828-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/11192960. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*