RNA is a notoriously unstable molecule. As a vaccine platform, mRNA came into prominence at the beginning of the 1990s because of its immunological features similar to those of live attenuated vaccines, such as endogenous antigen expression and T cell induction. At the same time, it has also got a defined composition and safety profile like that of a killed or subunit vaccine.
mRNAs are characterised by great flexibility with respect to production and application as a technological basis for therapeutics and vaccines. Any protein can be encoded and expressed by mRNA. When changes are effected by altering the sequence of the RNA molecule, it only impacts the encoded protein, and leaves its physico-chemical characteristics largely unaffected.
This feature allows mRNAs to be
utilised for manufacturing diverse products using the same established production process without any modifications. This reduces time and costs significantly compared to other vaccine platforms.
Unlike DNA, mRNA-based therapeutics do not need to cross the nuclear envelope to be effective. In contrast to peptides, mRNA vaccines lack major histocompatibility complex (MHC) haplotype restriction. mRNA can also bind to pattern recognition receptors. In addition, mRNA vaccines may be designed to be self-adjuvanting. This property is lacking in peptide- and protein-based vaccines.
On the other hand, mRNA is prone to rapid degradation by ubiquitous extracellular ribonucleases before being taken up by cells. Therefore, complexing agents are used to shield RNA from degradation. mRNA is often complexed with either lipids or polymers.
The first successful use of mRNA vaccines was reported in 1993, when a subcutaneous injection of liposome-encapsulated mRNA — encoding the nucleoprotein (NP) of influenza virus — was demonstrated to elicit NP-specific cytotoxic T cells (CTLs).
Researchers say mRNA presents a promising, if challenging, class of therapeutic molecules that has the potential to become the basis for “disruptive technology”.