Delivery of Circular mRNA via Degradable Lipid Nanoparticles against SARS-COV-2 Delta Variant

mRNA vaccines have emerged as a most promising and potent platform in the fight against various diseases including the COVID-19 pandemic. However, the intrinsic instability, varying side effects associated with the delivery systems, and continuous emergence of virus variants highlight the urgent need for the development of stable, safe and efficacious mRNA vaccines. In this study, by screening a panel of proprietary biodegradable ionizable lipidoids, we reported on a novel mRNA vaccine (cmRNA-1130) formed from a biodegradable lipidoid with eight ester bonds in the branched tail (AX4) and synthetic circular mRNA (cmRNA) encoding the trimeric Delta receptor binding domain (RBD) of SARS-CoV-2 spike protein for the induction of robust immune activation. The AX4-based lipid nanoparticles (AX4-LNP) revealed much faster elimination rate from liver and spleen in comparison with commercialized MC3-based LNP (MC3-LNP) and afforded normal level of alanine transferase (ALT), aspartate aminotransferase (AST), and creatinine (CRE) in BALB/c mice. Following intramuscular (IM) administration in BALB/c mice, cmRNA-1130 elicited potent and sustained neutralizing antibodies, RBD-specific CD4+ and CD8+ T effector memory cells (Tem), and Th1-biased T cell activations. cmRNA-1130 vaccine showed excellent stability against 6-month storage at 4 {degrees}C and freezing-thawing cycles. In brief, our study highlights mRNA vaccines based on cmRNA and biodegradable AX4 lipids hold great potential as superb therapeutic platforms for the treatment of varying diseases.

Inferior vena cava filter placement for the prevention of pulmonary embolism after deep vein thrombosis of lower extremities: Report of 14 cases / 中国微创外科杂志

Objective To evaluate the efficacy of inferior vena cava filter placement guided by digital subtraction angiography(DSA) for the prevention of pulmonary embolism(PE) after deep vein thrombosis(DVT) of the lower extremities.Methods Under the guidance of DSA,inferior vena cava filter placement was performed in 14 cases of deep vein thrombosis of the lower extremities from October 2003 to December 2004.Of the 14 cases,12 cases were given a simultaneous thrombectomy and 2 cases were treated conservatively.Results Filters were successfully placed in all the cases.The operation time was 85~115 min(mean,95 min).No complications were found during a follow-up of 1~14 months(mean,6 months).No recurrence of pulmonary embolism was seen included 5 patients who had survived previous pulmonary embolism attacks before the placement.Conclusions Inferior vena cava filter placement is a simple,safe,and effective method in the prevention of pulmonary embolism after deep vein thrombosis of the lower extremities.