Highlights of the 4th reporting period: The work is progressing according to plan. For the established frontrunner, i.e. lipid-based nanomedicines, we made sure that we can make exactly the same nanoparticles in different laboratories and also with different manufacturing technologies i.e. microfluidic mixing and rapid mixing. This is important as the production of the mRNA-based SARS-CoV2 vaccines has shown that rapid mixing appears to have become the new state-of-the-art.
Both on a QC as well as biological performance level, the lipid nanoparticles produced with both technologies were indistinguishable.
We have extended the work on the targeting nanobody that would enable translocation across the blood cerebrospinal fluid barrier. We established that the preferred 2HF042 nanobody can deliver a small peptide (i.e. neurotensin) over the blood cerebrospinal fluid barrier and functionally deliver this into the brain and are trying to determine the epitope to which it binds and determine what causes the translocation effect to occur. Several similar nanobodies do bind but lack the translocation phenomenon which is important to understand to be able to fully exploit.
In addition, we have made important progress with the emerging nanoparticles that for several application appear to outperform the lipid nanoparticles as state-of-the-art. Understanding the basis for this performance and specific conditions at which this occurs allows to sketch a path forward for future academic and industrial applications.
During the final period of the project, results have been validated and steps to be taken to enable exploitation after the project end have been prepared. The partners have analysed the results with a view to the TRL levels expected at the end of the project, IPR management and suitable exploitation routes. In summary, it can be said that we have
- identified nanobodies that are transported across the blood-cerebrospinal fluid barrier in mice and monkeys and can deliver a small payload (peptide). This can be exploited as a research reagent, especially in combination with the highly similar nanobodies that were identified that lack translocation capabilities. These can be immediately exploited.
- identified nanobodies and nanobody motifs for medical use. The identified nanobody sequences and motifs that dictate translocation will be patented. VIB will take the lead in this and establish the best route of exploitation, be it through a spin-off, or licensing opportunities.
- identified improvements in the composition of 20MED nanogels and coating technologies for the nanogels that will be pursued by 20MED.
- identified a novel composition of nanoemulsions that can carry and deliver siRNA (USC). USC will take the lead in protecting the invention.
- incorporated the technical expertise on the different nanocarriers (lipid nanoparticles, nanogels, nanoemulsions, nanoenvelopes, extracellular vesicles) into the design of equipment that can help R&D characterization of nanoparticles (MALVERN). This equipment is currently ready for beta-testing at partner sites (e.g. UMCU).
- made the design of a GMP plant (IBI) that can serve a service provider for the manufacture of GMP/GCP material for late preclinical and early clinical studies. This is important for the expansion of the field with many RNA formulations currently entering this stage of development.
- established a network within and beyond the consortium to initiate follow-up projects, several of these have already been established, such as H2020 EXPERT (UMCU, Eurice, SINTEF), Nanospresso-NL (SINTEF, UMCU)
