Consider the huge advances being made in nanomedicine, and the growth of a few giants whose products are perfectly matched to the emerging needs of the COVID-19 pandemic. Their juggernaut continues, with little indication it will slow.
A key driver is the opportunities to use the multitude of RNAs (e.g. mRNA, siRNA) in the treatment of many currently untreatable diseases. These uses are becoming a reality largely due to the capacity to encapsulate RNA for delivery in a form that can circumvent the body’s defences.
The promise of local manufacture, led more by scientific endeavour and less by the profit matrix of pharmaceutical giants, calls for an elegant disruptor in nanoparticle production, something that not only encapsulates RNA and other molecules in the laboratory but does so seamlessly and efficiently at scale. Micropore Technologies, a UK-based company with its roots in micromixing and emulsions, is expanding developments in the fundamental understanding of crossflow mixing technology research at Loughborough University. Engineers, scientists and pharma process control experts are designing a new way to solve the scaling production puzzle by developing advanced crossflow (AXF) mixing technology. It ticks all the fundamental boxes for the production of nanoparticles, such as mixing rates being faster than assembly rates and mixing being in laminar flow – and importantly it is not limited by volume.
This technology brings the possibility of producing vaccines for a multitude of diseases at a rate of 1500 litres an hour – about 58 000 doses every minute – from something that could fit into a small briefcase (youtu.be/1aaNwVTFCFg). To give context – the annual global production of Pfizer’s COVID vaccine in 2021 was three billion doses. Just one AXF mixer (the AXF-7) could arguably create the same number of doses in six months.
Precision-engineered, crossflow micromixing equipment allows for thorough, reproducible nanoformulation at scales ranging from microlitres up to hundreds of litres, using gentle laminar flows. The intuitive design and stainless-steel construction make good manufacturing practice (GMP) production of narrowly dispersed, accurately sized nanomedicines easier than ever before. Given the small footprint required and the simplicity of design, it is likely this will be the future of production; there is no need to build a factory. This technology makes a deal of sense: in a GMP setting, it is clean in place or steam in place, making it possible to achieve without the need to continuously buy consumables at exorbitant prices of hundreds of thousands of dollars just to run a single batch of just 50 or 100 litres.
In her review of current and emerging mRNA technologies (bit.ly/3JSOIcY), Jennifer Huen of Beagle Scientific concluded ‘Although IJM [impinging jet mixers – used by Pfizer in COVID vaccine production] is currently the encapsulation method of choice for mRNA vaccine manufacturers, the economic and environmental potential for advanced crossflow in gene therapies, RNA/DNA vaccines, protein-based drugs, and other biologics cannot be overlooked’. She also noted, ‘The scalability of crossflow mixing made it possible to develop a single instrument that covers the volumes needed from discovery to the clinical phase’.
Thanks to nanoformulation and microfluidics, Australia is on the cusp of local manufacturing of genetic medicines on a scale never seen before, with opportunities for global, equitable access, research and infrastructure to fit the evolving RNA science ecosystem.
The importance of RNA science to Australia (bit.ly/40DTS3k) has been highlighted by the beginnings of the UNSW RNA Institute. On 20 February, the New South Wales government of the day announced that Australia’s first RNA research and pilot manufacturing facility will be built at Macquarie University and operated by Myeloid Therapeutics, headed by CEO Dr Daniel Getts.
From the very early days of planning, the now New South Wales shadow Minister for Health The Hon Brad Hazzard worked tirelessly to bring this facility to fruition, probably before my letter in 2020 discussing the need to create a genetic medicine manufacturing ecosystem was forwarded to him by The Hon Gabrielle Upton. In a media release, Hazzard stated, ‘Investing in RNA research and manufacturing will ensure New South Wales remains a world leader in the development of medical technologies and therapeutics, which will ultimately deliver better patient outcomes, particularly for cancer and rare genetic diseases’. Let’s hope the new government will advance this initiative. Down the Hume in Canberra, the Shine–Dalgarno Centre for RNA Innovation integrates world-leading RNA biology research with advanced enabling infrastructure, allowing us to meet future biomedical challenges in partnership with industry, government and academia (bit.ly/3lUvThn). They are continuing work first described 50 years ago in the Nature article ‘Conserved terminal sequence in 18S rRNA may represent terminator anticodons’ (bit.ly/3lK6p6t). This ribosomal binding site in bacterial mRNA became known as the Shine–Dalgarno sequence, and the impact of such RNA science research and innovation is the subject of the Shine–Dalgarno Symposium, to be held 5–7 June.
The RNA science ecosystem continues to grow, with the Queensland government announcing a partnership with healthcare giant Sanofi to create a global mRNA vaccine hub (bit.ly/42IxzLv). This capacity building complements the brilliant work of the Translational Research Institute, Griffith University and the University of Queensland (including the BASE facility, which builds mRNA vaccines and therapies).
Continued funding from the Victorian government, the location of Moderna, Pfizer and the new CSL facilities – coupled with the existing excellence at Monash University, the Monash Institute of Pharmaceutical Sciences, the University of Melbourne, the Doherty Institute, CSIRO, St Vincent’s Institute, the Hudson Institute of Medical Research and RNA Victoria – means that RNA science in Victoria is incredibly strong too. Let us not forget the Australian and New Zealand RNA Production Consortium – the original driving force of these incredible developments (bit.ly/3LVsE3W). I met the original team during lockdowns over many Zoom meetings, developing strategies and creating connections with government, public servants with the aim to develop a genetic medicine manufacturing ecosystem in Australia. They were recognised in the Sydney Morning Herald’s ‘Australians who mattered’ in 2021 (bit.ly/3N1oLus).
New South Wales has brought together about a dozen institutions to work in collaboration; this is not a simple task. How do we shape this into a national approach? I can only echo the sentiments of an Australia leader in RNA science, Associate Professor Traude Beilharz of Monash University: ‘Without significant incentives from government, most of us would be driven by the career-metrics of our institutions/funders, which, despite all the talk of collaboration, still favour the “hero” who does everything by themselves’. A federal government approach to fund and assist in national strategy would encourage collaborative research, ensuring we play to our strengths without replicating effort while identifying the gaps in state investment, building a truly national world-class ecosystem that can mobilise at times of patent need.
What all this suggests is that Australia is well on the way to a thriving industry in RNA science, and that with a little more effort it can set a global benchmark.