RNA vaccine

Dendritic cells (DCs) are a type of immune cells that display antigens on their surfaces, leading to interactions with T cells to initiate an immune response. DCs can be collected from patients and be programmed with mRNA. Then, they can be re-administered back into patients to create an immune response.[14]

Since the discovery of in vitro transcribed mRNA expression in vivo following direct administration, in vivo approaches have become more and more attractive.[15] They offer some advantages over ex vivo methods, most significantly by avoiding the cost of harvesting and adapting DCs from patients and by imitating a regular infection. However, there are multiple obstacles for these methods that are yet to be overcome for RNA vaccination to be a potent procedure. Evolutionary mechanisms that prevent the infiltration of unknown nucleic material and promote degradation by RNases should be avoided in order to initiate translation. In addition, the mobility of RNA on its own is completely dependent on regular cell processes because it is too heavy to diffuse, consequently it is bound to be eliminated, halting translation.

The mode of mRNA uptake has been known for over a decade,[16][17] and the use of RNA as a vaccine tool was discovered in the 1990s in the form of self-amplifying mRNA.[18] It has also emerged that the different routes of injection, such as into the skin, blood or to muscles, resulted in varying levels of mRNA uptake, making the choice of administration route a critical aspect of delivery. Kreiter et al. demonstrated, in comparing different routes, that lymph node injection leads to the largest T cell response.[19] It should be kept in mind that the mechanisms and consequently the evaluation of self-amplifying mRNA could be different, as they are fundamentally different by being a much bigger molecule in size.[1]

The idea of encapsulating mRNA in lipid nanoparticles has been attractive for a number of reasons.[20] Principally, the lipid provides a layer of protection against degradation, allowing more robust translational output. In addition, the customization of the lipid outer layer allows the targeting of desired cell types through ligand interactions. However, many studies have also highlighted the difficulty of studying this type of delivery, demonstrating that there is an inconsistency between in vivo and in vitro applications of nanoparticles in terms of cellular intake.[21] The nanoparticles can be administered to the body and transported via multiple routes, such as intravenously or through the lymphatic system.