mRNA vaccines — a new era in vaccinology

In the citing paper

“mRNA production and lipid nanoparticle formulation are fast and highly scalable, which renders this technology suitable for the rapid development and supply of vaccines during pandemic scenarios 11,12 .”

In the citing paper

“samRNA vaccines can induce potent immune responses at lower doses due to their ability to amplify antigen production within the body, potentially reducing the risk of adverse reactions6,44.”

In the citing paper

“In particular, we focused on ψ and m1ψ, since these substitutions for U have been widely adopted for mRNA therapeutics and vaccines due to improved in-cell translation and to better control of innate immune responses2,3,8,67 through avoidance of recognition by cellular toll-like receptors (TLR7 and TLR8)68, RIG‑I, and PKR69–71.”

In the citing paper

“The technique can be easily scaled requiring minimum platform changes during mRNA formulation and production (Pardi et al. 2018).”

In the citing paper

“which is widely believed to be critical to the recent success of mRNA vaccines1,2,10,37,38”

In the citing paper

“The mRNA also does not interact with the genome and only the parts directly required for the encoded protein expression are present in this basic genetic construct (Pardi et al. 2018).”

In the citing paper

“Both BNT162b2 and mRNA-1273, as well as the adenoviral-vectored vaccine ChAdOx1 nCoV-19, have been shown to induce type I interferon, thus potentially inducing pathogen-agnostic protection75–77.”

In the citing paper

“Non-replicating mRNA vaccines deliver exclusively genetic information coding for the target antigen, thus containing the 5′-cap, 5′ untranslated region (UTR), 3′ UTR, and 3′-poly(A) tail regions.108”

In the citing paper

“Furthermore, the upscaling of cell-free vaccine production is relatively straightforward, thereby providing a cutting-edge tool for rapid response in epidemics and pandemics.4, 5, 6, 7”

In the citing paper

“Unlike some viral vaccines, mRNA does not integrate into the genome, obviating concerns about insertional mutagenesis5.”

In the citing paper

“The use of modified nucleosides, particularly modified uridine, prevents recognition by pattern recognition receptors, enabling sufficient levels of translation to produce prophylactic amounts of protein5.”

In the citing paper

“although it has been employed for various therapeutic targets, its use as a source of antigen in vaccination approaches is by far the most popular [2]”

In the citing paper

“mRNA has shown therapeutic potential in a range of applications, including viral vaccines, protein replacement therapies, cancer immunotherapies, cellular reprogramming and genome editing2,4,7–17.”

In the citing paper

“mRNA normally contains five structural elements, that is, a 5′ cap, a 3′ poly(A) tail, a protein-coding sequence and 5′ and 3′ untranslated regions (UTRs)2,4,7,13.”

In the citing paper

“mRNA is susceptible to degradation and, thus, formulation buffers should be free of any ribonuclease contaminations2,4.”

In the citing paper

“These elements can be engineered to improve the stability and translational efficiency of mRNA2,4,7,13.”

In the citing paper

“Chromatographic purification can remove double-stranded RNA, an analogue of viral genome, in IVT mRNA preparations, diminishing immune activation and increasing translational efficiency2,4,7,183.”

In the citing paper

“Chemical modifications of specific IVT mRNA nucleotides, such as pseudouridine (ψ) and N1-methylpseudouridine (m1ψ), can reduce innate immune sensing of exogenous mRNA translation2,4,7,182.”

In the citing paper

“Many other lipid nanoparticle–mRNA formulations are in clinical trials for the treatment of infectious diseases, cancer and genetic disorders2,4,8,12–14 (Tables 1,2).”

In the citing paper

“These features make lipid nanoparticle–mRNA formulations a flexible and on-demand vaccine platform to rapidly respond to emerging infectious pathogens4,15,17.”

In the citing paper

“To address these concerns, the engineering of mRNA molecules (Box 1) and the design of lipid nanoparticles have been optimized2,4,7–17, which has contributed to the rapid development and clinical assessment15,17 of the two COVID-19 mRNA vaccines, mRNA-1273 (NCT04470427)19,20 and BNT162b2 (NCT04368728)21.”

In the citing paper

“Since then, lipid nanoparticle–mRNA formulations have emerged as a potent alternative to conventional vaccine platforms, owing to their unique features4,15,17.”

In the citing paper

“Moreover, mRNA-based cellular reprogramming, tissue regeneration and genome editing have shown therapeutic potential in preclinical studies2,4,8,12–14.”

In the citing paper

“First, mRNA is a non-infective and non-integrating agent with the ability to encode a broad range of antigens4,15,17.”

In the citing paper

“Finally, GMP-grade lipid nanoparticle-mRNA vaccines can be manufactured for specific antigens in a short period of time, compared with other vaccine platforms, such as recombinant proteins and inactivated vaccines2,4,15,17.”

In the citing paper

“Neoantigens are often different between individual patients, allowing the development of personalized vaccines4,11.”

In the citing paper

“Neoantigens, generated by somatic mutations in cancer cells, are usually tumour-specific and have high immunogenicity4,11.”

In the citing paper

“The sequences of these elements regulate translation initiation, translation termination and post-transcriptional modification of mRNA molecules2,4.”

In the citing paper

“To achieve effective translation, mRNA requires five structural elements, including the 5′ cap, 3′ poly(A) tail, protein-coding sequence and 5′ and 3′ untranslated regions (UTRs)2,4.”

In the citing paper

“the application of RNA vaccines has been limited by their lack of stability and requirement for a cold chain”

In the citing paper

“RNA vaccines, for example, have exhibited encouraging results in both infection therapy and cancer immunotherapy.[6, 7, 11–15]”

In the citing paper

“mRNA functions as the bridge between DNA and proteins in eukaryotic cells.[8, 12, 119]”