How do mammalian cells handle mRNA therapeutics: Optimising the molecular basis of manufacture

哺乳动物细胞如何处理 mRNA 疗法：优化制造的分子基础

• 批准号: 2903763
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2903763
• 关键词: How; do; mammalian; cells; handle

The use of mRNA to generate vaccines against COVID-19 has cemented the potential for nucleic acids to develop approaches to prevent viral infection and to have wider applications in the treatment of life-threatening cancers (Nature [2021] 589: 189-191; The Lancet [2022] 23: e450-e458). To maximise the potential of mRNA (and other nucleic acid-based therapeutics) we need to understand more about their delivery into cells, intracellular handling/stability and the processes that link cellular localisation to effective expression. We also need to determine if findings are generic to cell types or if processes can be optimised for specific cell types and status. This provides the overall aim for your project. The specific objectives of your project will require you to (i) generate a panel of mRNA products (ii) examine the uptake, processing and expression within a panel of cultured mammalian cells, (iii) screen host cell phenotype in response to the extent of product expression, (iv) use machine learning methods to understand changes in metabolic pathways upon uptake of mRNA products by mammalian cells and (v) test hypotheses derived by engineering specific cellular functionalities. In achieving these objectives you will master a wide range of analytical, cellular and molecular techniques, including fluorescence microscopy, high resolution mass spectrometry assays, omics data interrogation, chemometrics methods, data interpretation and cellular and process engineering. Working with the Centre for Process Innovation (CPI) RNA Centre of Excellence (https://www.uk-cpi.com/about/national-centres/rna-centre-of-excellence) we will be part of a wider vision to innovate design and manufacture of RNA vaccines and therapeutics.

使用mRNA对COVID-19产生疫苗，巩固了核酸开发预防病毒感染的方法的潜力，并在威胁生命的癌症治疗中更广泛地应用（自然[2021] 589：189：189-191; Lancet [2022] 23：E450-E450-E458）。为了最大程度地提高mRNA（和其他基于核酸的治疗剂）的潜力，我们需要更多地了解它们输送到细胞，细胞内处理/稳定性以及将细胞定位与有效表达联系起来的过程。我们还需要确定发现发现是否对细胞类型是一般性，或者是否可以针对特定的单元类型和状态进行优化。这为您的项目提供了总体目标。 The specific objectives of your project will require you to (i) generate a panel of mRNA products (ii) examine the uptake, processing and expression within a panel of cultured mammalian cells, (iii) screen host cell phenotype in response to the extent of product expression, (iv) use machine learning methods to understand changes in metabolic pathways upon uptake of mRNA products by mammalian cells and (v) test hypotheses derived by engineering specific cellular功能。在实现这些目标时，您将掌握广泛的分析，细胞和分子技术，包括荧光显微镜，高分辨率质谱分析，OMICS数据询问，化学计算方法，数据解释以及细胞和过程工程。与过程创新中心（CPI）RNA卓越中心（https://www.uk-cpi.com/about/national-centres/rna-centres/rna-centre-of-excellence）合作，我们将成为RNA疫苗和治疗学的创新设计和制造的更广阔视野的一部分。