The rapid clinical success of mRNA vaccines during the SARS-CoV-2 pandemic was largely driven by ionisable lipid nanoparticle (LNP) delivery vehicles. These LNPs help to activate the immune system and enable efficiency intracellular delivery while protecting the mRNA from degradation1. mRNA vaccines have now shown success in treating other viruses and infectious diseases, including cancer. The LNP formulation becomes a key determinant in the immune response outcome.
Efficacy in cancer vaccines requires a robust CD8+ T cell response to recognise and destroy tumour cells. This response is highest in the spleen where antigen-presenting cells are in close proximity to adaptive immune cells2. However, the conventional LNP formulation accumulates in the liver3.
One recent strategy to alter biodistribution utilised manipulation of the protein corona. This is a layer of protein that adsorbs around the nanoparticle in vivo, influencing cellular uptake and specific organ targeting4. The isolation and characterisation of the protein corona can inform the development of spleen-tropic LNP formulation. This research involves the investigation into corona isolation methods as well as the validation of assays to ensure accuracy of results.
1. Chaudhary, N., Weissman, D. & Whitehead, K. A. mRNA vaccines for infectious diseases: principles, delivery and clinical translation. Nat. Rev. Drug Discov. 20, 817–838 (2021).
2. Kranz, L. M. et al. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature 534, 396-401J (2016).
3. Akinc, A. et al. The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs. Nat. Nanotechnol. 14, 1084–1087 (2019).
4. Dilliard, S. A., Cheng, Q. & Siegwart, D. J. On the mechanism of tissue-specific mRNA delivery by selective organ targeting nanoparticles. Proc. Natl. Acad. Sci. 118, e2109256118 (2021).