TY - JOUR T1 - Delivery of Circular mRNA via Degradable Lipid Nanoparticles against SARS-CoV-2 Delta Variant JF - bioRxiv DO - 10.1101/2022.05.12.491597 SP - 2022.05.12.491597 AU - Ke Huang AU - Na Li AU - Yingwen Li AU - Jiafeng Zhu AU - Qianyi Fan AU - Jiali Yang AU - Yinjia Gao AU - Yuping Liu AU - Qiangbo Hou AU - Shufeng Gao AU - Ke Wei AU - Chao Deng AU - Chijian Zuo AU - Zhenhua Sun Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/05/13/2022.05.12.491597.abstract N2 - 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 °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.Competing Interest StatementThe authors have declared no competing interest. ER -