Liquid Brain: Revolutionising prediction of the in vivo pharmacokinetics and biodistribution of mRNA-lipid nanoparticles

Lipid nanoparticles (LNPs) are sub-micron-scale spherical vesicles made of ionisable lipids. They are used to safely and effectively deliver drugs including nucleic acids such as messenger RNA (mRNA) to target cells, most prominently being deployed in Pfizer-BioNTech and Moderna's mRNA-based COVID-19 vaccines. Although receiving increasing attention, LNPs are complex to design, since they are typically composed of at least four lipid components: (i) ionisable cationic lipids (to ensure effective cell penetration and cargo release in the cytoplasm); (ii) helper lipids (to promote cell binding); (iii) cholesterol (to pack out the lipids); and, (iv) a polyethylene glycol (PEG)-lipid conjugate (to improve stability).

This results in a large combinatorial space, since the individual components and the relative ratios of each must be optimised for each new therapeutic application and administration route.

High-throughput assembly and in vitro screening technologies for LNPs permit traversing of this combinatorial space, cost-effectively manufacturing and analysing thousands of novel LNPs. Yet, because of time and cost constraints, only a limited number of LNPs (often, only 5-10) can be taken forward to preclinical in vivo studies. These LNPs are selected based on the results of cell-based in vitro assays.

However, studies have shown that there is no correlation between in vitro and in vivo results. In other words, the in vitro models do not accurately represent in vivo behaviour. This results in high failure rates for novel LNPs at preclinical in vivo stage, increasing development costs and reducing R&D efficiency for BioTech/Pharma.

Founded in 2021 by Dr Shamit Shrivastava (experimental physicist and inventor of Apoha's core platform technology; previously postdoctoral researcher at the University of Oxford) and Anshika Srivastava (skilled in operating and scaling businesses; previously Executive Director/Vice President, Goldman Sachs), Apoha is a seed-stage start-up based in London, UK. Our mission is to empower scientists to design materials with new functional properties inspired by the physics of brain matter.

Founded in 2009 by PD Dr Carsten Rudolph (lead inventor of Ethris' core mRNA platform technology) and Professor Christian Plank (biochemist with expertise in targeted drug delivery), Ethris is a clinical-stage BioTech based in Munich, Germany. Ethris' mission is to redefine mRNA medicines through best-in-industry delivery, stability, and nebulization technology.

Here, Apoha and Ethris will leverage the unique complementary skills and expertise of both partners to address the in vitro/in vivo predictability challenge of LNPs, reducing development costs and increasing BioTech/Pharma R&D efficiency.