Nature子刊：江绍毅团队开发具有低反应原性和高肿瘤抗原表达的mRNA-LNP癌症疫苗

Core Viewpoint - The article discusses the development of a novel mRNA cancer vaccine utilizing membrane-destabilizing zwitterionic lipids, which addresses two major challenges: limited mRNA expression and unavoidable inflammatory responses [2][4]. Group 1: Research Development - A research team led by Professor Jiang Shaoyi from Cornell University published a study in Nature Biomedical Engineering, highlighting a new mRNA cancer vaccine that exhibits low reactogenicity and high tumor antigen expression [3]. - The study introduces a membrane-destabilizing zwitterionic lipid that enhances mRNA expression by promoting endosomal escape while simultaneously reducing inflammatory responses [6]. Group 2: Lipid Characteristics - The zwitterionic lipid features a pyridinium carboxybetaine (PyCB) head group, a biodegradable multi-tail alkyl chain, and a tertiary amine linker, which allows for effective protonation and biocompatibility under physiological pH conditions [6]. - The PyCB head group forms a zwitterionic PyCB-water complex, which becomes positively charged at pH levels below 6.8, facilitating efficient mRNA release in endosomes [6]. Group 3: Enhanced Vaccine Efficacy - Incorporating this zwitterionic lipid into commercial mRNA vaccine LNP formulations significantly increases mRNA expression levels in antigen-presenting cells within lymph nodes, thereby enhancing cytotoxic T cell activation [7]. - The zwitterionic nature of the lipid results in reduced inflammatory responses and neutrophil infiltration at the injection site, providing an advantage for the nanoparticles containing this lipid [7]. - This lipid is also compatible with existing targeted nanoparticle formulations, which can further optimize mRNA delivery efficiency [7].