RAP-IDD - Rapid Development of Intracellular Drug Delivery Innovations

rapp - idd项目（细胞内药物递送创新的快速发展）由英国SME Micropore Technologies （Micropore）领导，由SME Labman Automation （Labman）和CPI支持，旨在开发和验证一种新的技术平台，将基因组物质（RNA和DNA）封装在保护性纳米颗粒中，并将其与高通量表征相结合。在现有方法的基础上，该平台将升级为连续生产，使其适用于高通量配方开发和符合良好生产规范（GMP）的连续生产。如果成功，这个新平台将使新的基因组药物从发现到疾病预防和治疗的实际应用的效率有一个阶梯性的提高。在2019冠状病毒病大流行期间，基于mrna的疫苗取得了成功，这使得人们对通过纳米颗粒递送系统递送到细胞中的其他核酸药物的兴趣大大增加。目前正在研究类似的技术，以实现针对其他疾病的突破性疫苗，以及针对癌症、罕见疾病等的靶向治疗。然而，纳米递送细胞内药物的成功开发和制造仍然存在障碍。将核酸包封在保护性纳米颗粒（NPs）内，如脂质纳米颗粒（LNPs），可能是制造过程中最关键的阶段。目前使用的封装技术主要有两种：在研究中，微流控混合装置常用，因为它们可以快速生成大型配方库，同时最大限度地减少浪费。然而，这些混合器不能适应商业规模的产量。选择撞击射流混合（IJM）技术作为在COVID大流行期间实现大规模商业生产的可用手段，通过将多个单元并行堆叠。然而，这种方法不太可控，而且对发现来说是浪费和低效的。Micropore正在开拓一种名为Advanced Crossflow （AXF）的替代专利微混合/封装技术，该技术将微流体方法的尺寸控制和均匀性优势与扩展到商业体积的能力相结合，只需增加仪器尺寸和物料流量。RAP-IDD项目将以AXF技术为基础，以实现细胞内药物生产的“圣杯”为目标：一个单一、高效、灵活的多产品技术平台，可以跨越药物开发和生产途径的多个阶段——从实验室规模到商业规模——而无需在不同阶段重新开发和重新优化流程。该项目将进行研究以降低风险并验证这一方法。

The RAP-IDD project (Rapid Development of Intracellular Drug Delivery Innovations), led by the UK SME Micropore Technologies (Micropore), supported by SME Labman Automation (Labman) and CPI, aims to develop and validate a new technology platform to encapsulate genomic material (RNA and DNA) in protective nanoparticles and integrate this with high-throughput characterisation. In a game-changing advance over current methods, the platform will be upgraded to continuous production to make it applicable to both high-throughput formulation development and continuous manufacturing - compliant with Good Manufacturing Practice (GMP). If successful, this new platform will make a step-change improvement in the efficiency with which new genomic medicines progress from discovery to real application in disease prevention and treatment.The success of mRNA-based vaccines during the COVID-19 pandemic has resulted in a large increase in interest in other nucleic acid medicines that are delivered to cells via nanoparticle delivery systems. Similar technologies are being researched to enable breakthrough vaccines for other diseases, as well as targeted treatments for cancer, rare diseases and more. However, there remain barriers to successful development and manufacture of nanodelivered intracellular drugs. The encapsulation of the nucleic acids within protective nanoparticles (NPs), such as lipid nanoparticles (LNPs), is perhaps the most critical stage in the manufacturing process. Currently there are two major encapsulation technology approaches used: In research, microfluidic mixing devices are commonly used as they can quickly produce large formulation libraries while minimizing waste. However, these mixers cannot accommodate commercial-scale production volumes. Impingement jet mixing (IJM) technology was chosen as an available means to achieve large scale commercial production during the COVID pandemic, by stacking many units in parallel. However, this approach is less controllable and is wasteful and inefficient for discovery.Micropore is pioneering an alternative and patented micromixing/encapsulation technology called Advanced Crossflow (AXF) that combines the size-control and uniformity advantages of microfluidic approaches with an ability to scale up to commercial volumes, simply by increasing instrument size and material flow. The RAP-IDD project will build on this AXF technology with the aim of achieving the 'holy grail' of intracellular drug production: A single, highly-efficient, but flexible, multi-product technology platform that can span multiple phases of the drug development and production pathway -- from lab scale to commercial scale -- without the need to redevelop and re-optimise processes at different stages. The project will undertake research to de-risk and validate this approach.