Lipid nanoparticles as delivery system for mRNA have recently attracted attention to a broader audience as COVID-19 mRNA vaccines. Their low immunogenicity and capability to deliver a variety of nucleic acids renders them an interesting and complementary alternative to gene therapy vectors like AAVs. An important quality attribute of LNPs is the copy number of the encapsulated cargo molecule. This work describes how density and molecular weight distributions obtained by density contrast sedimentation velocity can be used to calculate the mRNA copy number of a degradable lipid nanoparticle formulation. The determined average copy number of 5 mRNA molecules per LNP is consistent with the previous studies using other biophysical techniques, such as single particle imaging microscopy and multi-laser cylindrical illumination confocal spectroscopy (CICS).

作为 mRNA 递送系统的脂质纳米颗粒最近作为 COVID-19 mRNA 疫苗吸引了更广泛受众的关注。它们的低免疫原性和传递多种核酸的能力使它们成为 AAV 等基因治疗载体的有趣且互补的替代品。 LNP 的一个重要质量属性是封装的货物分子的拷贝数。这项工作描述了如何使用通过密度对比沉降速度获得的密度和分子量分布来计算可降解脂质纳米颗粒制剂的 mRNA 拷贝数。确定的每个 LNP 5 个 mRNA 分子的平均拷贝数与之前使用其他生物物理技术的研究一致，例如单颗粒成像显微镜和多激光圆柱照明共焦光谱 (CICS)。