RAP-IDD - Rapid Development of Intracellular Drug Delivery Innovations

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.