Manufacturing the Future of Nanomedicine

EU-funded RNA-based therapy targets the direct cause of some neurodegenerative diseases, not just their symptoms.

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The EU-funded B-SMART project, established to treat a range of neurodegenerative conditions, has taken a significant step towards this aim by selecting a platform to manufacture its nanomedicines.

Precision NanoSystem’s NanoAssemblr™ will use RNA-based therapeutics to stem disease producing proteins for conditions such as Parkinson’s, Alzheimer’s and Huntington’s. These illnesses affect over seven million people across Europe, with a socio-economic burden previously estimated at around 130 billion euros per year.

Overcoming the barrier to RNA therapy

RNA is a molecule influential in the coding, decoding, regulation and expression of genes, which includes the production of proteins responsible for disease. There has been much excitement at the prospect of co-opting this function (through messenger RNA – mRNA) to enable medicine to instruct the body to stop damage before it occurs. This is a relatively new field of medicine, only going back a couple of decades and considered safer and more cost-effective than alternative genetic manipulation options.

However, for these RNA modalities to reach their full potential, they first need to overcome the body’s defences, developed through billions of years of evolution. Protections such as lipid bilayers (forming a thin membrane) have served to keep the RNAs on the outside of cells from being able to easily get inside cells. Overcoming this armoury has remained, quite literally, a barrier to the widespread development of RNA therapeutics.

B-SMART has developed just such an effective delivery mechanism through the use of ‘nanocarriers’. These are transport modules small enough to cross the brain-cerebrospinal fluid barrier while also protecting the RNA enzymes against degradation.

As the B-SMART project coordinator, Professor Raymond Schiffelers, summarises in a recent ‘Technology Networks’ article announcing the selection of the manufacturing platform, ‘RNA medicines are interesting because you can use what is essentially the same polynucleotide molecule to treat multiple diseases, just by changing the nucleotide sequence. Our goal is therefore to design modular nanoparticles capable of delivering a payload of therapeutic RNAs to the brain, allowing them to prevent the biosynthesis of harmful proteins at source.’

Out of the lab and into clinics

To increase effectiveness, the delivery mechanism required specific targeting using ligands (small molecules, ions or proteins), based on heavy chain-only nanobodies, which are smaller and more stable than conventional antibodies. The modular delivery system is being tested both in vitro and in vivo.

Taking advantage of knowledge gleaned form the multidisciplinary field of microfluidics, and key to getting B-SMART’s approach out of the lab and into a wide range of European therapeutic settings, is the development of a scalable and reproducible manufacturing process. Towards this end the benchtop NanoAssemblr platform will be in use in the eight laboratories involved in the project, across the Netherlands, Belgium, Norway, the UK, Spain and Italy.

Professor Schiffelers further explains the selection of the Precision NanoSystem’s NanoAssemblr platform by saying, ‘This technology also allows you to accurately predict the particle size based on the mixing speed, PEG [polyether compounds] concentration and mixing ratios, which is a significant step forward. Equally importantly, it can be easily scaled to manufacture batch volumes sufficient for clinical trials’. The pre-clinical efficacy will be tested after local injection, nasal administration and systemic administration.

Source: CORDIS