mRNA vaccines can be developed when a population may be affected by epidemics⁵ or pandemics to help protect against disease in a broad range of individuals across the world.⁶ In this instance, mRNA may encode an antigen that induces an immune response against the targeted pathogen.⁷

It may be possible to include more than one mRNA, each encoding for different pathogen proteins in a single vaccine, which may be referred to as a multivalent vaccine depending on how many proteins it targets.⁸

Example preclinical investigation
In 2023, researchers published preclinical research on two mRNA vaccines against Pseudomonas aeruginosa encoding the full-length of PcrV, a component of the type III secretion system in Pseudomonas spp., and a fusion protein of the outer membrane proteins OprF and OprI, respectively.⁹ mRNA for each vaccine was packaged into lipid nanoparticles (LNPs). Mice vaccinated with these mRNA-LNPs produced IgG antibodies against all encoded antigens. These results may lead to the potential development of new vaccines for Pseudomonas aeruginosa.⁹

Advances in sequencing techniques may allow assessment of genetic mutations within individuals.⁴ For instance, only a subset of a group of patients may have a disease-driving mutation, awareness of which might allow for different treatment options to be attempted.¹⁰

Mutant epitopes, for example, can drive cancer immunity; however, only a small fraction of mutations are recognized by the immune system in patients with tumors.¹¹ mRNA technology may enable the design of mRNA sequences for individual patients who have such mutations, to encode proteins that may mobilize the immune system and generate cell-mediated immune responses.⁴

The outcome of this could be to induce the suppression or removal of cells bearing the targeted mutations, potentially reducing the tumor burden.^4,11

Example preclinical investigation
A 2022 preclinical research publication demonstrated that the injection of dendritic cells containing mRNA encoding personalized tumor neoantigens and an ovarian cancer-associated antigen resulted in no formation of any detectable tumors compared with a positive control in a murine cancer model.¹²

Protein replacement therapy aims to substitute or replenish specific proteins that are deficient – either absent or nonfunctional – due to mutations in affected individuals.¹³ mRNA technology may potentially be employed to produce mRNA that encodes a protein that is deficient.¹³

Once translated, the protein can participate in biological processes, potentially reducing the effect of the protein deficiency. The concept of using mRNA to replace proteins intracellularly was first evaluated in preclinical investigations: Diabetes insipidus was temporarily reversed in rats through the introduction of hormone-encoding mRNA.¹⁴

Example preclinical investigation
Arginase deficiency is an inherited metabolic liver disease that can lead to developmental delays, psychomotor function loss, and, uncommonly, death.¹⁵ In 2019, research showed that administration of LNPs encapsulating optimized mRNA encoding for arginase led to an improved survival rate compared with mice treated with control LNPs.¹⁵ This research highlighted that delivery of mRNA is a potential strategy to help in restoring missing or defective enzyme function.¹⁵

mRNA may be able to help reprogram cells through the synthesis of proteins involved in the transcriptional regulation of gene expression.¹⁶ Encoding for proteins such as transcription factors may allow for alterations in gene expression that ultimately lead to cellular reprogramming and cell regeneration.¹⁷

This regeneration may allow the restoration of deficient or absent cellular functions, which in turn might restore tissue function in patients with diseased or damaged organs.¹⁷

Example preclinical investigation
In 2018, researchers used mRNAs encoding for reprogramming factors, including SOX2, KLF4, cMYC, LIN28A, and NANOG, to reprogram human cell lines.^17,18 Results showed that multiple normal and disease-specific human fibroblast cell lines could be reprogrammed into induced pluripotent stem cells, which can differentiate into a vast array of different cell types.^17,18 This work may expand the possible future potential clinical applications of mRNA in the treatment of diseased or aging tissues.^17,18