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Diana D Kang^1,2, Xucheng Hou¹, Leiming Wang¹

¹Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

Bioactive materials

|March 25, 2024

概括

聚糖 (pSar) 脂质在脂质纳米颗粒 (LNP) 中为mRNA输送提供了聚乙烯糖醇 (PEG) 脂质的有希望的替代品. 用pSar取代PEG可以保持或提高mRNA传递效率和安全性,解决对抗PEG抗体的担忧.

科学领域:

生物技术是生物技术.
纳米医学是一种纳米医学.
疫苗开发疫苗开发

背景情况:

脂质纳米颗粒 (LNP) 对于mRNA疫苗的输送至关重要,特别是对于SARS-CoV-2疫苗.
目前的LNP配方使用聚乙烯糖醇 (PEG) 脂质,可以引起抗PEG抗体.
反PEG抗体可能导致不良反应和治疗效果降低.

研究的目的:

在LNP配方中研究聚沙可素 (pSar) 脂质作为PEG脂质的潜在替代品.
评估pSar脂质是否可以在已建立的LNP系统中保留PEG脂质的功能性质 (ALC-0315和SM-102).
评估基于pSar的LNP用于mRNA输送的安全性和有效性.

主要方法:

合成和表征了LNP配方,其中不同比例的psar脂质取代了PEG脂质.
评估了mRNA封装和体外释放动力学.
在临床前模型中评估了体内mRNA递送效率和生物分布.
监测免疫反应和与PEG和pSar成分相关的潜在不良影响.

主要成果:

在ALC-0315和SM-102 LNP系统中,可以将PEG脂质完全替换为psar脂质.
与基于PEG的LNP相比,基于pSar的LNP显示出可比或增强的mRNA传递效率.
发现含有pSar的LNP的体内安全性概况与传统含有PEG的LNP相似.
与pSar脂质合并时没有观察到不良反应的显著增加.

结论:

聚沙可素 (pSar) 脂质是通过脂质纳米粒子 (LNP) 传递mRNA的聚乙烯糖醇 (PEG) 脂质的可行的替代品.
基于psar的LNP保持或改善mRNA传递的有效性,并表现出良好的安全性,减轻了与抗PEG抗体相关的担忧.
这些发现支持开发下一代LNP配方,用于具有潜在降低免疫原性的mRNA疗法和疫苗.

关键词:

脂质纳米颗粒的使用方法聚乙烯甘醇 (PEG) 是一种聚乙烯甘醇.聚糖氨酸 (pSar) 是一种多糖氨酸.它们是mRNARNA.

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