Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Development of a high-throughput platform for screening lipid nanoparticles for mRNA delivery
Nanoscale ( IF 5.8 ) Pub Date : 2022-01-05 , DOI: 10.1039/d1nr06858j Lili Cui 1 , Sara Pereira 1 , Silvia Sonzini 1 , Sally van Pelt 1 , Steven M Romanelli 2 , Lihuan Liang 3 , David Ulkoski 4 , Venkata R Krishnamurthy 4 , Emily Brannigan 5 , Christopher Brankin 5 , Arpan S Desai 1
Nanoscale ( IF 5.8 ) Pub Date : 2022-01-05 , DOI: 10.1039/d1nr06858j Lili Cui 1 , Sara Pereira 1 , Silvia Sonzini 1 , Sally van Pelt 1 , Steven M Romanelli 2 , Lihuan Liang 3 , David Ulkoski 4 , Venkata R Krishnamurthy 4 , Emily Brannigan 5 , Christopher Brankin 5 , Arpan S Desai 1
Affiliation
|
mRNA lipid nanoparticles (LNPs) are at the forefront of nucleic acid intracellular delivery, as exemplified by the recent emergency approval of two mRNA LNP-based COVID-19 vaccines. The success of an LNP product largely depends on the systematic optimisation of the four lipidic components, namely the ionisable lipid, PEG lipid, structural and helper lipids. However, the in vitro screening of novel lipidic components and LNP compositions is limited by the low-throughput of LNP preparation. To address these issues, we herein present an automated high-throughput screening platform to select novel ionisable lipids and corresponding LNPs encapsulating mRNA in vitro. This high-throughput platform employs a lab-based automated liquid handling system, amenable to high-throughput (up to 384 formulations per plate and several plates per run) and allows precise mixing and reproducible mRNA LNP preparation which ensures a direct head-to-head comparison of hundreds and even thousands of novel LNPs. Most importantly, the robotic process has been successfully applied to the screening of novel LNPs encapsulating mRNA and has identified the same novel mRNA LNP leads as those from microfluidics-mixing technology, with a correlation coefficient of 0.8751. This high-throughput platform can facilitate to narrow down the number of novel ionisable lipids to be evaluated in vivo. Moreover, this platform has been integrated into a fully-automated workflow for LNP property control, physicochemical characterisation and biological evaluation. The high-throughput platform may accelerate proprietary lipid development, mRNA LNP lead optimisation and candidate selection to advance preclinical mRNA LNP development to meet urgent global needs.
中文翻译：
开发用于筛选用于 mRNA 递送的脂质纳米颗粒的高通量平台
mRNA 脂质纳米粒子 (LNP) 处于核酸细胞内递送的最前沿，最近紧急批准的两种基于 mRNA LNP 的 COVID-19 疫苗就是例证。 LNP 产品的成功很大程度上取决于四种脂质成分的系统优化，即可电离脂质、PEG 脂质、结构脂质和辅助脂质。然而，新型脂质成分和 LNP 组合物的体外筛选受到 LNP 制备低通量的限制。为了解决这些问题，我们在此提出了一个自动化高通量筛选平台，用于选择新型可电离脂质和体外封装 mRNA 的相应 LNP。该高通量平台采用基于实验室的自动化液体处理系统，适合高通量（每板最多 384 个配方，每次运行多个板），并允许精确混合和可重复的 mRNA LNP 制备，确保直接头对-对数百甚至数千种新型 LNP 进行头部比较。最重要的是，机器人过程已成功应用于封装mRNA的新型LNP的筛选，并鉴定出与微流控混合技术相同的新型mRNA LNP先导物，相关系数为0.8751。这种高通量平台可以有助于缩小体内待评估的新型可电离脂质的数量。此外，该平台已集成到 LNP 特性控制、理化表征和生物学评估的全自动工作流程中。高通量平台可以加速专有脂质开发、mRNA LNP 先导物优化和候选药物选择，以推进临床前 mRNA LNP 开发，以满足全球紧迫需求。
更新日期：2022-01-05
中文翻译：
开发用于筛选用于 mRNA 递送的脂质纳米颗粒的高通量平台
mRNA 脂质纳米粒子 (LNP) 处于核酸细胞内递送的最前沿，最近紧急批准的两种基于 mRNA LNP 的 COVID-19 疫苗就是例证。 LNP 产品的成功很大程度上取决于四种脂质成分的系统优化，即可电离脂质、PEG 脂质、结构脂质和辅助脂质。然而，新型脂质成分和 LNP 组合物的体外筛选受到 LNP 制备低通量的限制。为了解决这些问题，我们在此提出了一个自动化高通量筛选平台，用于选择新型可电离脂质和体外封装 mRNA 的相应 LNP。该高通量平台采用基于实验室的自动化液体处理系统，适合高通量（每板最多 384 个配方，每次运行多个板），并允许精确混合和可重复的 mRNA LNP 制备，确保直接头对-对数百甚至数千种新型 LNP 进行头部比较。最重要的是，机器人过程已成功应用于封装mRNA的新型LNP的筛选，并鉴定出与微流控混合技术相同的新型mRNA LNP先导物，相关系数为0.8751。这种高通量平台可以有助于缩小体内待评估的新型可电离脂质的数量。此外，该平台已集成到 LNP 特性控制、理化表征和生物学评估的全自动工作流程中。高通量平台可以加速专有脂质开发、mRNA LNP 先导物优化和候选药物选择，以推进临床前 mRNA LNP 开发，以满足全球紧迫需求。
京公网安备 11010802027423号