Lipid nanoparticle technology
Novel eTheRNA LNP
- NProprietary lipid combination
- NOptimized for systemic delivery
- NBiodistribution focused on the spleen
- NDesigned for cancer vaccines
We will combine exciting mRNA-based immunotherapies with cutting edge nanomedicine technologies. This nanomedicine has been designed following extensive research and innovation to deliver and express the mRNAs in dendritic cells residing mainly in the spleen.
It is driven by growing evidence of the advantages of IV administration of vaccine immunotherapies. Systemic administration of antigen-encoding mRNAs is a particularly potent way to induce high-magnitude antigen-specific CD8+ T-cell responses. Preclinical studies performed by eTheRNA have shown superiority in terms of efficacy compared to subcutaneous and intranodal administration in tumour models. Building on the preclinical and clinical successes to date, the ultimate goal of TIGER is the development of a TriMix-mRNA based immunotherapy suitable for IV application.
This ambition comes with its own challenges:
Systemic delivery of naked, unformulated mRNA results in fast enzymatic degradation (due to RNases in plasma).
mRNA has an inherent immunostimulatory effect that strongly activates the innate immune system. This in turn results in expression of proinflammatory cytokines and type I interferons (IFNs). Although this may be beneficial for the intended therapeutic outcome, an overactivation of innate immunity may lead to unfavourable safety profiles and toxicity. A careful balance between immune activation, efficacy and safety is required.
Due to mRNA’s physicochemical properties, including the large size and negative charge, mRNAs face multiple extracellular and intracellular barriers.
Address these challenges
To address these challenges, a robust delivery vehicle is required.
We explored various options and have now developed a patented proprietary LNP delivery system for IV administration of encapsulated mRNAs (mRNA-LNP).
The LNP enables the vehicle to: