Ischemic heart disease (IHD) is the leading cause of death worldwide. According to the World Health Organization, patients die of IHD account for 16% of the world's total population every year (The top 10 causes of death (who.int). Myocardial infarction (MI) is one of the main manifestations of IHD. It induces myocardial necrosis or apoptosis in a short time, which lead to heart failure, and exhibits poor prognosis. MI is listed as the leading cause of death in IHD. Although methods such as clinical revascularization and drug therapy have been applied to improve coronary perfusion in the ischemic myocardium region of MI patients, there are still a considerable number of patients who are not suitable for percutaneous or surgical revascularization. In recent years, therapeutic angiogenesis has been proposed as a new strategy for the treatment of MI. Angiogenesis is the core repair method of the heart, and promoting vascular repair at the infarcted site has important theoretical and clinical application value for MI treatment.

Vascular endothelial growth factor A (VEGF-A) performs excellently in MI treatment as it plays prominent roles in promoting angiogenesis, recruiting and homing stem cells,reducing apoptosis, increasing vasodilation and regulating autonomic responses. Studies have included direct administration of VEGF-A (protein therapy), promotion of VEGF-A gene expression in vivo (gene therapy), delivery of stem cells (cell therapy) or exosomes (cell-free therapy) and other forms of treatment. VEGF-A have received extensive attention due to its potential beneficial effects in cardiovascular disease, but the clinical efficacy is not as satisfactory due to multiple factors such as suboptimal pharmacokinetics, low local protein concentration, poor gene transfer efficiency and inappropriate doses. To circumvent the problems associated with recombinant proteins and gene therapy, mRNA has been proposed for its advantages of high tissue specificity, safety, rapidity, and long expression duration. The VEGF-A protein, which is expressed by highly purified, non-immunogenic, optimized clinically produced mRNA, can solve the existing drawbacks and give full play to its function.

Compared with traditional linear mRNA, circular mRNA has inherent advantages such as simpler preparation process, longer expression duration and lower immunogenicity. CureMed has a new type of circular mRNA,cmRNA, with independent intellectual property rights, and has verified its advantages of long-term high expression and lower immunogenicity in multiple animal models. CureMed's previous researches have verified that mRNA can be expressed at a high level in the infarcted marginal area of MI animals. After one administration of mRNA, a significant improvement in cardiac EF and FS indicators can be observed on the 14th day, and at the same time the infarcted area can be significantly reduced.

At present, AstraZeneca's AZD8601 project that uses modified linear mRNA to express VEGF-A has completed the Phase II clinical trials, where the prognosis of coronary artery disease patients with surgical revascularization was improved through therapeutic angiogenesis. Although the results have not yet been published, preclinical studies and Phase I clinical results have sent positive signals.