Developing Lipid Nanoparticles for the delivery of mRNA.

信使核糖核酸（mRNA）疫苗的有效性现已得到充分证明，导致使用脂质纳米颗粒递送的基于mRNA的COVID-19疫苗的使用。脂质纳米颗粒（LNP）是这些疫苗的关键组分，因为它们保护mRNA免于在体内降解并介导递送到细胞的细胞质中。通常，LNP由各种比例的中性结构脂质、胆固醇、PEG-脂质（以控制粒度）和可电离脂质（其在低pH下是阳离子的，因此结合mRNA，并且在生理pH下具有近中性电荷）组成。然而，在设计最佳mRNA-LNP制剂时，有广泛的选择需要考虑，并且所选择的脂质选择的影响尚未得到很好的理解。因此，该项目的目的是支持与细胞内药物递送卓越中心（ICDDC）和CPI一起实施用于mRNA递送的LNP的筛选和表征。这将涉及：1）LNP的高通量制备，2）LNP的高通量分析表征和3）快速效力筛选工具。该计划的可交付成果将是实施该筛选，以优化LNP，从而识别铅制剂，显著节省时间和资源，并降低早期LNP制剂开发的风险。

The efficacy of messenger ribonucleic acid (mRNA) vaccines is now well demonstrated, leading to the use of mRNA-based COVID-19 vaccines delivered using lipid nanoparticles. Lipid nanoparticles (LNPs) are a key component of these vaccines as they protect the mRNA from degradation in the body and mediate delivery into the cytoplasm of cells. Generally, LNPs are comprised of various ratios of a neutral structural lipid, cholesterol, a PEG-lipid (to control particle size), and an ionisable lipid (which is cationic at low pH and thus binds the mRNA, and near-neutral charge at physiological pH). However, there is a wide range of choices to consider when designing an optimal mRNA-LNP formulation, and the impact of the lipid choice selected is not well understood. Therefore, the aim of this project is to support the implementation of screening and characterisation of LNPs for mRNA delivery in conjunction with the IntraCellular Drug Delivery Centre of Excellence (ICDDC) and CPI. This will involve: 1) high-throughput preparation of LNPs, 2) high-throughput analytical characterisation of LNPs and 3) rapid potency screening tools. This deliverable of this programme will be the implementation of this screening to optimise LNPs which identifies lead formulations, provides significant savings in time and resources and de-risks early-stage LNP formulation development.