mRNA Sonotransfection of Tumors with Polymeric Microbubbles: Co-Formulation versus Co-Administration.

Despite its high potential, non-viral gene therapy of cancer remains challenging due to inefficient nucleic acid delivery. Ultrasound (US) with microbubbles (MB) can open biological barriers and thus improve DNA and mRNA passage. Polymeric MB are an interesting alternative to clinically used lipid-coated MB because of their high stability, narrow size distribution, and easy functionalization. However, besides choosing the ideal MB, it remains unclear whether nanocarrier-encapsulated mRNA should be administered separately (co-administration) or conjugated to MB (co-formulation). Therefore, the impact of poly(n-butyl cyanoacrylate) MB co-administration with mRNA-DOTAP/DOPE lipoplexes or their co-formulation on the transfection of cancer cells in vitro and in vivo is analyzed. Sonotransfection improved mRNA delivery into 4T1 breast cancer cells in vitro with co-administration being more efficient than co-formulation. In vivo, the co-administration sonotransfection approach also resulted in higher transfection efficiency and reached deeper into the tumor tissue. On the contrary, co-formulation mainly promoted transfection of endothelial and perivascular cells. Furthermore, the co-formulation approach is much more dependent on the US trigger, resulting in significantly lower off-site transfection. Thus, the findings indicate that the choice of co-administration or co-formulation in sonotransfection should depend on the targeted cell population, tolerable off-site transfection, and the therapeutic purpose.

Overexpression of GAS5 inhibits abnormal activation of Wnt/ß-catenin signaling pathway in myocardial tissues of rats with coronary artery disease.

OBJECTIVE: The aim of this study is to investigate the clinical value of long noncoding RNA growth arrest-specific transcript 5 (LncRNA GAS5) in the diagnosis of coronary artery disease (CAD) and its protective effect on myocardial injury in rats with CAD. METHODS: Patients with CAD and healthy controls were selected to measure the expression of GAS5, and further to perform the correlation analysis and ROC curve. In addition, the rat models of CAD were also established to observe the effect of GAS5 on hyperlipidemia, myocardial injury, cardiomyocyte apoptosis, oxidative stress, and inflammatory injury of rats with CAD, and the effect of the Wnt/ß-catenin signaling pathway was also determined. RESULTS: Overexpression of GAS5 in CAD rats determines improvement of hyperlipidemia, attenuation of myocardial injury, inhibition of cardiomyocyte apoptosis, oxidative stress, inflammatory injury, and abnormal activation of the Wnt/ß-catenin signaling pathway in myocardial tissues. CONCLUSION: Our study demonstrates that downregulation of GAS5 is found in CAD, and overexpression of GAS5 inhibits abnormal activation of the Wnt/ß-catenin signaling pathway in myocardial tissues of CAD rats.