mRNA therapeutics is a rapidly expanding area of research within various medical applications, ranging from vaccines to cancer treatments. First widely adopted into the mainstream as a prevention tool for avoiding severe illness from SARS Cov2, mRNA is now being explored as a way to address genetic disorders and various forms of cancer. By encoding CRISPR machinery to be translated into cells or by training the immune system to attack cancerous cells, mRNA is fast becoming a powerful treatment tool for gaining access to traditionally undruggable targets. As the formulation chemistries that enable mRNA to be effective at expressing therapeutic proteins race forward, there are two major challenges currently limiting its full clinical potential. The first is the generalized inability to effectively target mRNA to specific cell types using standard LNPs, and the second, even more limiting challenge, is mRNA’s inability to efficiently reach the cytosol of cells once targeted to a specific cell type. Here, we will review aspects of the first challenge with regard to current methods of targeting mRNA, introducing new emerging platforms that seek to incorporate antibodies, aptamers, and small molecules as targeting agents. We highlight ways in which these critical challenges are being addressed and what future formulation designs seek to enable in order to achieve a more controlled delivery of this important biomolecule.
Pal et al. (Thu,) studied this question.