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Cited by 203RNA and protein synthesis mechanismsSARS-CoV-2 and COVID-19 ResearchRNA Interference and Gene Delivery

Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines

Open access
Xia, Xuhua·2021·Vaccines
DOI 10.3390/vaccines9070734PMC PMC8310186
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Abstract

The design of Pfizer/BioNTech and Moderna mRNA vaccines involves many different types of optimizations. Proper optimization of vaccine mRNA can reduce dosage required for each injection leading to more efficient immunization programs. The mRNA components of the vaccine need to have a 5′-UTR to load ribosomes efficiently onto the mRNA for translation initiation, optimized codon usage for efficient translation elongation, and optimal stop codon for efficient translation termination. Both 5′-UTR and the downstream 3′-UTR should be optimized for mRNA stability. The replacement of uridine by N1-methylpseudourinine (Ψ) complicates some of these optimization processes because Ψ is more versatile in wobbling than U. Different optimizations can conflict with each other, and compromises would need to be made. I highlight the similarities and differences between Pfizer/BioNTech and Moderna mRNA vaccines and discuss the advantage and disadvantage of each to facilitate future vaccine improvement. In particular, I point out a few optimizations in the design of the two mRNA vaccines that have not been performed properly.

AI snapshot

Written from the paper’s full text.

TL;DR

Xia dissects the design of Pfizer/BioNTech BNT-162b2 and Moderna mRNA-1273, comparing 5′-UTRs, codon optimization, translation initiation, termination signals, and 3′-UTRs. He argues several optimizations are suboptimal—especially Moderna’s CGG codon choice and both vaccines’ UGA-containing stop signals—while noting some interpretations remain uncertain.

Key findings

  • Both vaccines increased CGN Arg codons and reduced AGR codons: BNT-162b2 reduced AGR by 8 and mRNA-1273 by 28; highly expressed ribosomal protein genes encode 64.2% of Arg by CGN. However, the paper argues CGG is not the optimal CGN codon: highly expressed skeletal muscle genes prefer CGC over CGG (paired t-test, t = 3.075, DF = 25, p = 0.0034), and mRNA-1273 overused CGG.
  • BNT162b2 uses the human α-globin 5′-UTR with Kozak GCCACCAUG and little secondary structure flanking the start codon; mRNA-1273 has a GC-rich element and secondary structure with MFE −12.3 for the 40-nt window around the start codon, versus −11.1 for α-globin. The paper says BNT162b2’s 5′-UTR appears superior but cautions that 8.6% of ribosomal protein genes have MFE equal to or smaller than −12.3.
  • BNT162b2 ends with UGAUGA and mRNA-1273 with UGAUAAUAG; the paper argues the optimal stop signal should be UAAA, because UGA is leakiest and highly expressed RP genes favor +4R (likelihood ratio chi-square = 931.0514, DF = 17, p < 0.000001). Ψ substitution may further increase stop-codon misreading and +1 frameshifting.
  • Given 100 μg mRNA-1273 versus 30 μg BNT-162b2 and equivalent efficacy, the paper infers Pfizer/BioNTech mRNA may produce about 3.3 times as many proteins per mRNA. CAI values are 0.94925 for BNT-162b2 and 0.97939 for mRNA-1273, but higher CAI is not necessarily better because Moderna used a “fundamentalist” and Pfizer/BioNTech a “liberal” codon strategy.

Methods

  • Sequence data included 33 RPS and 50 RPL ubiquitously expressed ribosomal protein genes, 11,327 annotated CDSs from human chromosome 1, intron nucleotide frequencies from chromosomes 18–22, SARS-CoV/SARS-CoV-2 and related coronavirus genomes, and vaccine mRNA sequences (BNT-162b2 public; mRNA-1273 putative from Jeong et al., with UTRs matching Moderna patents).
  • Tissue expression used Human Protein Atlas data from 62 tissues; top 50 skeletal-muscle highly expressed genes were selected, with 26 having CDSs ≥300 codons for Table 2; ZAP expression was extracted from three HPA files.
  • Analyses used DAMBE for CDS extraction, codon frequencies, CAI, ITE, PWM, and MFE (Vienna RNA fold); SARS-CoV-2 transcriptomic SRA SRR11886744 was analyzed for subgenomic spike mRNA; statistical tests included paired t-test and likelihood ratio test.

Limitations

  • Stated: the mRNA-1273 sequence is putative and “should be considered putative,” though its UTRs match Moderna patents; there is no systematic evaluation of the fundamentalist versus liberal codon optimization strategies in translation efficiency; the 5′-UTR secondary-structure interpretation is cautioned because some highly expressed genes have comparable MFE; and Ψ replacement complicates stop-codon reasoning.
  • Evident: the study is computational/in silico and reports no new wet-lab translation or immunogenicity experiments; inferences about dosage, protein output, and translation efficiency are indirect.
  • Evident: the paper itself notes that tRNA gene copy number is problematic as a proxy for tRNA abundance because nearly half of human tRNA genes are not expressed.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/vaccines9070734

Cites

93 of 93 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

44 of 136 cited sources checked · 10 supported · 4 flagged · accuracy not yet measured

  • Premisecitation

    The effect of +4G and downstream nucleotides on translation initiation has been inconclusive.

    “First, while the -3R (site 4 in the first column of Table 5) has been demonstrated repeatedly to enhance translation initiation, the effect of +4G (site 10 in Table 5), as well as nucleotides downstream, on translation initiation has been inconclusive [46,49,50,51].”
    Quote in the paperSubstantial claim2 of 4 sources checked
    • cites [46] Kozak, 1999, Initiation of translation in prokaryotes and eukaryotes, Gene source
    • cites [49] Kozak, 2001, A progress report on translational control in eukaryotes, Sci. STKE source
    • cites [50] Kozak, 2003, Not every polymorphism close to the AUG codon can be explained by invoking context effects on initiation of translation, Blood source

      In the letter “Not every polymorphism close to the AUG codon can be explained by invoking context effects on initiation of translation,” Kozak says mutagenesis experiments found that +4G makes one of the strongest contributions to translation initiation. That is contrary to describing the effect of +4G as inconclusive. The References section also identifies a study reporting that +4G augments initiation, while nucleotides at +5 and +6 generally do not affect it. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [51] Kozak, 1997, Recognition of AUG and alternative initiator codons is augmented by G in position +4 but is not generally affected by the nucleotides in positions +5 and +6, Embo J. source

      The paper does not leave the effect of +4G inconclusive: the Discussion says its positive effect is generalizable, while the results report no significant effect from changes at +5 or +6 in the tests described. It notes a sequence-specific exception to the usual +4G effect, but presents that as an exception rather than an inconclusive overall finding (Discussion; Figures 4–6, page not provided in our copy). (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation

    There is little evidence that +4G and downstream nucleotides contribute to translation initiation.

    “There is little evidence that +4G and downstream nucleotides contribute to translation initiation.”
    Quote in the paperSubstantial claim2 of 4 sources checked
    • cites [46] Kozak, 1999, Initiation of translation in prokaryotes and eukaryotes, Gene source
    • cites [49] Kozak, 2001, A progress report on translational control in eukaryotes, Sci. STKE source
    • cites [50] Kozak, 2003, Not every polymorphism close to the AUG codon can be explained by invoking context effects on initiation of translation, Blood source

      In the letter “Not every polymorphism close to the AUG codon can be explained by invoking context effects on initiation of translation” (page not supplied), Kozak says that G at +4 makes one of the strongest contributions to start-codon recognition. The paper also says downstream secondary structure can compensate for a suboptimal initiation context. Its caution about a particular −1 polymorphism does not support the broad claim that there is little evidence for a contribution from +4G. (LLM, conf=0.90)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [51] Kozak, 1997, Recognition of AUG and alternative initiator codons is augmented by G in position +4 but is not generally affected by the nucleotides in positions +5 and +6, Embo J. source

      The Discussion reports little or no effect from varying nucleotides at +5 and +6, supporting that part of the claim. But it also reports a strong, generalizable contribution of G at +4 to initiator-codon recognition, contrary to the claim about +4G. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
  • Premisecitation

    Translation initiation is often the rate-limiting step.

    “Optimum codon usage without efficient translation initiation does not increase protein production [10,11] because translation initiation is often the rate-limiting step.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [10] Tuller, 2010, Translation efficiency is determined by both codon bias and folding energy, Proc. Natl. Acad. Sci. USA source

      The Discussion and Conclusions (page unavailable) say that, for individual genes in the E. coli and S. cerevisiae transcriptomes studied, codon bias—not folding energy at the start of a gene—is the rate-limiting factor. The paper discusses effects on initiation, but its own conclusion does not support the citing sentence’s claim that initiation is often rate-limiting. (LLM, conf=0.83)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [11] Xia, 2015, A Major Controversy in Codon-Anticodon Adaptation Resolved by a New Codon Usage Index, Genetics source

      The Conceptual Framework says that inefficient initiation can limit the benefit of improved codon adaptation. But the Discussion concludes that both initiation and elongation limit translation efficiency, and notes that the low-initiation group studied is not representative of most genes. The paper therefore does not establish that initiation is often the rate-limiting step. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
  • Premisecitation

    When nucleotide U in stop codons was replaced by Ψ, the rate of misreading of a stop codon by a near-cognate tRNAs increased.

    “When nucleotide U in stop codons was replaced by Ψ, the rate of misreading of a stop codon by a near-cognate tRNAs increased [17].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [17] Adachi, 2019, Post-transcriptional pseudouridylation in mRNA as well as in some major types of noncoding RNAs, Biochim. Et Biophys. Acta. Gene Regul. Mech. source

      In “Targeted pseudouridylation promotes stop codon read-through” (page unavailable), the review reports that replacing U with Ψ promotes stop-codon read-through and describes tRNA anticodon pairing during decoding. It does not report a measured increase in the rate of misreading by near-cognate tRNAs specifically. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Premisecitation

    S-2P differs from the spike protein in the reference SARS-CoV-2 genome (NC_045512) by two amino acids, i.e., amino acids KV at sites 986 and 987 were replaced by PP.

    “Both mRNA encodes the same S-2P protein [5,6] which differ from the spike protein in the reference SARS-CoV-2 genome (NC_045512) by two amino acids, i.e., amino acids KV at sites 986 and 987 were replaced by PP to stabilize the resulting spike protein in the prefusion state to train the host immune system to recognize the virus before its entry into the host cell [7,8].”
    Quote in the paperNot a substantial claim4 of 4 sources checked
    • cites [5] Anderson, E.J., Rouphael, N.G., Widge, A.T., Jackson, L.A., Roberts, P.C., Makhene, M., Chappell, J.D., Denison, M.R., Stevens, L.J., and Pruijssers, A.J. (2020). Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults. N. Engl. J. Med. source

      The Methods section (‘mRNA-1273 Vaccine’; page not provided) says S-2P contains two proline substitutions, and the Discussion describes them as prefusion-stabilizing mutations. Our copy does not identify the original residues as KV, give positions 986 and 987, or specify the reference genome accession NC_045512. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [6] Jackson, 2020, An mRNA Vaccine against SARS-CoV-2-Preliminary Report, N. Engl. J. Med. source

      The Methods (Vaccine; page not provided) state that S-2P has two proline substitutions at positions 986 and 987, stabilizing the spike protein in its prefusion conformation. Our copy does not identify the original amino acids as KV or specify the reference genome accession NC_045512. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [7] Hsieh, 2020, Structure-based design of prefusion-stabilized SARS-CoV-2 spikes, Science source

      The supplied passage describing S-2P (section labeled Abstract; page unavailable) says it contains two consecutive proline substitutions in the S2 subunit that stabilize the prefusion spike. Our copy does not identify the original residues as KV, give positions 986 and 987, or compare the construct with reference genome NC_045512, so those specifics are not verified. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [8] Xia, X. (2021). Domains and Functions of Spike Protein in SARS-COV-2 in the Context of Vaccine Design. Viruses, 13. source
  • Classified as probably not a substantial claim. 16
  • May combine two claims. 41
  • The quote only partly states this claim. 1

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    mRNA vaccines have many different but convenient routes for vaccine administration, including subcutaneous, intramuscular, intradermal, intratracheal, intravenous and intraperitoneal routes.

    “This highlights one advantage of mRNA vaccines because it has many different but convenient routes for vaccine administration, including subcutaneous, intramuscular, intradermal, intratracheal, intravenous and intraperitoneal routes [31].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [31] Pardi, 2015, Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes, J. Control. Release source

      The Discussion lists all six routes used to deliver nucleoside-modified mRNA-LNPs, and the Abstract reports protein expression after administration to mice. The study tested luciferase expression, not vaccine administration or whether these routes are convenient for vaccination. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Translation initiation is typically the limiting step in translation, and its efficiency depends heavily on how rapidly the 5′-UTR can load ribosome onto the mRNA.

    “Translation initiation is typically the limiting step in translation, and its efficiency depends heavily on how rapidly the 5′-UTR can load ribosome onto the mRNA [9].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [9] Xia, 2011, Translation Initiation: A Regulatory Role for Poly(A) Tracts in Front of the AUG Codon in Saccharomyces cerevisiae, Genetics source

      The Abstract (page not provided) calls the 5′-UTR a ribosome-loading dock during initiation and a key site of translation regulation. The Results section on protein synthesis rate and ribosomal density (page not provided) uses ribosomal density as a measure of translation efficiency. Neither passage establishes that initiation is typically the limiting step or that efficiency depends specifically on the speed of ribosome loading. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Ψ is more promiscuous in base-pairing than U and can pair with both A and G and, to a lesser extent, with C and U, so stop codons become more prone to misreading by tRNAs.

    “As Ψ is more promiscuous in base-pairing than U and can pair with both A and G and, to a less extent, with C and U [16], stop codons become more prone to misreading by tRNAs [17].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [16] Kierzek, 2014, The contribution of pseudouridine to stabilities and structure of RNAs, Nucleic Acids Res. source

      The Discussion reports Ψ-A, Ψ-G and Ψ-U hydrogen bonding and generally greater stability when Ψ replaces U in mispairs. But it says Ψ and U hydrogen-bond to those bases in similar ways, and finds no NMR evidence of hydrogen bonding in Ψ-C, so the claimed greater breadth of base-pairing is not established. The stop-codon clause is attached to a different citation and is not judged here. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [17] Adachi, 2019, Post-transcriptional pseudouridylation in mRNA as well as in some major types of noncoding RNAs, Biochim. Et Biophys. Acta. Gene Regul. Mech. source

      The Introduction (page unavailable) says Ψ has an additional hydrogen-bond donor and chemical properties distinct from U, but does not specify that Ψ pairs with A and G or, less readily, C and U. The stop-codon read-through section reports decoding of pseudouridylated stop codons, but the citing sentence attaches a separate citation to that consequence. (LLM, conf=0.80)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Similar predictions can be made for +5 or +6 sites, but their effect on translation termination is far less consistent than the +4 site.

    “Similar predictions can also be made with respect to +5 or +6 sites which, however, have their effect far less consistent than the +4 site on translation termination [65].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [65] McCaughan, 1995, Translational termination efficiency in mammals is influenced by the base following the stop codon, Proc. Natl. Acad. Sci. USA source

      The Results report that the fifth base has little effect on a strong UGAA termination signal but affects a weak UGAC signal, supporting a context-dependent effect compared with the experimentally established fourth-base effect. The paper notes a statistical bias at the sixth position and cites possible importance in Sindbis virus RNA, but does not establish that sixth-base effects on translation termination are less consistent than fourth-base effects. Page numbers are unavailable in our copy. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The binding affinity to eRF1 is in the order of UAA > UGA and UAG, suggesting that UAA is a more efficient stop codon than the other two.

    “First, the binding affinity to eRF1 is in the order of UAA > UGA and UAG [63,64], suggesting that UAA is a more efficient stop codon than the other two.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [63] Konecki, 1977, Characterization of reticulocyte release factor, J. Biol. Chem. source
    • cites [64] Tate, 1973, Influence of Guanine Nucleotides and Elongation Factors on Interaction of Release Factors with the Ribosome, Proc. Natl. Acad. Sci. USA source

      The Results (Fig. 3; page not specified) show that tetranucleotides containing all three stop codons competed in a reticulocyte release-factor binding assay, and that UAGA required a higher concentration for complete competition. The paper does not establish the claimed UAA > UGA affinity ordering or show that UAA is a more efficient stop codon; it also notes contamination affecting the UAGA result. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The translation termination signal is more than a stop codon, including the downstream +4 site (tetranucleotide stop signal).

    “It has long been recognized that the translation termination signal is more than a stop codon [86,87], leading to an early proposal of tetranucleotide stop signal including the downstream +4 site [63,65,87,88].”
    Quote in the paperNot a substantial claim1 of 5 sources checked
    • cites [86] Tate, 1992, Translational termination: “stop” for protein synthesis or “pause” for regulation of gene expression, Biochemistry source
    • cites [87] Tate, 1996, Three, four or more: The translational stop signal at length, Mol. Microbiol. source
    • cites [63] Konecki, 1977, Characterization of reticulocyte release factor, J. Biol. Chem. source
    • cites [65] McCaughan, 1995, Translational termination efficiency in mammals is influenced by the base following the stop codon, Proc. Natl. Acad. Sci. USA source
    • cites [88] Brown, 1990, Sequence analysis suggests that tetra-nucleotides signal the termination of protein synthesis in eukaryotes, Nucleic Acids Res. source

  • May combine two claims.

    Premisecitation

    Such +1 frameshifting also occurs in eukaryotes, such as the mammalian AZ1 gene with a stop codon context UGAU, where the first U is often skipped when polyamine concentration is high, resulting in the ribosome reading GAU as the next codon.

    “Such frameshifting also occurs in eukaryotes, such as the mammalian AZ1 gene with a stop codon context UGAU [85], where UGA is the stop codon followed by a U at the +4 site. The first U in the stop codon in translating AZ1 mRNA is often skipped when the concentration of polyamines is high, resulting in the ribosome reading GAU as the next codon [85].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [85] Namy, 2004, Reprogrammed genetic decoding in cellular gene expression, Mol. Cell source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S4 (based).

    Findingnone given

    The SARS-CoV-2 reference genome (NC_045512) has 34 GAA codons and 14 GAG codons in its spike protein gene.

    “The SARS-CoV-2 reference genome (NC_045512) has 34 GAA codons and 14 GAG codons in its spike protein gene.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    Pfizer/BioNTech's BNT162b2 mRNA and Moderna's mRNA-1273 share the same amino acid sequence but differ in many other ways, such as the design of 5′-UTR, codon optimization and 3′-UTR.

    “While the Pfizer/BioNTech’s BNT162b2 mRNA and Moderna’s mRNA-1273 share the same amino acid sequence, they differ in many other ways, such as the design of 5′-UTR, codon optimization and 3′-UTR.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The putative sequence of mRNA-1273 is the real mRNA-1273.

  • May combine two claims.

    Findingreasoning

    The designers of both vaccines considered CGG as the optimal codon in the CGN codon family and recoded almost all CGN codons to CGG.

    “The designers of both vaccines considered CGG as the optimal codon in the CGN codon family and recoded almost all CGN codons to CGG.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    BNT-162b2 and mRNA-1273 reduced AGR codons by 8 and 28, respectively, with the corresponding increase in CGN codons.

    “BNT-162b2 and mRNA-1273 reduced AGR codons by 8 and 28, respectively, with the corresponding increase in CGN codons.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The putative sequence of mRNA-1273 is the real mRNA-1273.

  • May combine two claims.

    Findingown data

    SARS-2-S in the reference genome (NC_045512) contains 42 Arg residues, of which 30 are encoded by AGR codons and only 12 are encoded by CGN codons.

    “For example, SARS-2-S in the reference genome (NC_045512) contains 42 Arg residues, of which 30 are encoded by AGR codons and only 12 are encoded by CGN codons (SRef column in Table 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The S gene from natural coronaviruses has CAI < 0.7 for their spike protein CDS, but the two codon-optimized spike CDSs have CAI equal to 0.94925 and 0.97939, respectively.

    “The S gene from natural coronaviruses have CAI < 0.7 for their spike protein CDS, but the two codon-optimized spike CDSs have CAI equal to 0.94925 and 0.97939, respectively (Table 4).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    For 2-fold R-ending codons, background mutation bias favors A-ending codons, but ribosomal protein genes consistently favor G-ending codons in every 2-fold R-ending codon family.

    “For 2-fold R-ending codons, background mutation bias, as reflected by nucleotide frequencies of introns in human genome, favors A-ending codons, but ribosomal protein genes consistently favor G-ending codons in every 2-fold R-ending codon family.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    Moderna consistently applied the fundamentalist strategy for all codon families in mRNA-1273, whereas Pfizer/BioNTech consistently used the liberal strategy in codon optimization for BNT-162b2.

    “Moderna has consistently applied the fundamentalist strategy for all codon families in mRNA-1273, whereas Pfizer/BioNTech has consistently used the liberal strategy in codon optimization for BNT-162b2.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Findingnone given

    The frequency of nucleotide G is consistently higher than that of C in human introns.

    “(The frequency for nucleotide G is consistently higher than that of C in human introns).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    A human genome contains seven tRNAArg/ACG genes, four tRNAArg/CCG genes, and six tRNAArg/UCG genes.

    “A human genome contains seven tRNAArg/ACG genes (where superscripted ACG is the anticodon, with A deaminated to inosine I) to decode CGY codons, four tRNAArg/CCG genes to decode CGG codons and six tRNAArg/UCG genes to decode CGA and CGG (through wobble pairing at third codon site).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Findingnone given

    mRNA-1273 has a problem in codon optimization, including excessive use of CGG that is not an optimal codon.

    “As I mentioned before, mRNA-1273 also has a problem in codon optimization (e.g., excessive use of CGG that is not an optimal codon).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The 40-nt window for the human α-globin gene has an MFE of −11.1, indicating only a slightly weaker secondary structure relative to the corresponding region in mRNA-1273 with an MFE value of −12.3.

    “For example, the 40-nt window (with 20 nt before the start codon AUG and 20 nt in the 5′ end of CDS) for human α-globin gene has an MFE of −11.1, indicating only a slightly weaker secondary structure relative to the corresponding region in mRNA-1273 with an MFE value of −12.3.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    The optimal Kozak consensus is GCCACCAUG, which is used to replace the original ACCAUG in BNT162b2.

    “As shown before in Table 5, the optimal Kozak consensus is GCCACCAUG which is used to replace the original ACCAUG (Figure 2A).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Findingnone given

    Mammalian highly expressed genes are typically far more GC-rich in sequences flanking the start codon than lowly expressed genes, so the former tend to have more stable secondary structure than the latter.

    “However, mammalian highly expressed genes are typically far more GC-rich in sequences flanking the start codon than lowly expressed genes, so the former tend to have more stable secondary structure than the latter.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    The 5′-UTR in Moderna's mRNA-1273 is made of two elements: the first is SEQ ID NO 1 in a list of 16,120 sequences in one patent, followed by a GC-rich second element CCCCGGCGCC just before the Kozak consensus ACCAUG.

    “It is made of two elements. The first element is SEQ ID NO 1 in a list of 16,120 sequences in one patent [19]. This element is followed by a GC-rich second element CCCCGGCGCC [18], just before the Kozak consensus ACCAUG.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [19] De Fougerolles, A., and Guild, J. (2020). Modified Polynucleotides for the Production of Secreted Proteins. (US 10,703,789 B2), U.S. Patent.

      Not checked in the free run.

    • cites [18] Huang, E.Y.-C., Tse, S.-W., Iacovelli, J., McKinney, K., and Valiante, N. (2021). Immunomodulatory Therapeutic mRNA Compositions Encoding Activating Oncogene Mutation Peptides. (US 10,881,730 B2), U.S. Patent.

      Not checked in the free run.

  • May combine two claims.

    Findingreasoning

    The two mRNA vaccines both used GCCACCAUG, but not the codon after the start codon AUG.

    “The two mRNA vaccines both used GCCACCAUG, but not the codon after the start codon AUG, for two good reasons.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Findingreasoning

    The difference in GC-richness between highly expressed and lowly expressed genes is true both in the 5′-UTR immediately upstream of the coding sequence and in the 3′-UTR immediately downstream of the coding sequence.

    “This difference in GC-richness between highly expressed and lowly expressed genes is true both in 5′-UTR immediately upstream of the coding sequence and in 3′-UTR immediately downstream of the coding sequence.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The site-specific pattern consistent with the GCCRCCAUGG consensus is consistent for genes from other human chromosomes and is stronger in highly expressed genes than in lowly expressed genes.

    “This pattern is consistent for genes from other human chromosomes, and stronger in highly expressed genes than lowly expressed genes.”
    Quote in the paperNot a substantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    There are 11,327 annotated Chr01 CDSs (including isoforms), and consequently 11,327 stop codons, including 3306 UAA, 2578 UAG and 5443 UGA stop codons.

    “There are 11,327 annotated Chr01 CDSs (including isoforms), and consequently 11,327 stop codons. These includes 3306 UAA, 2578 UAG and 5443 stop codons (Table 7).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The hypothesis that highly expressed genes favor +4R is strongly supported, consistent across all three stop codons (Table 7).

    “The hypothesis that highly expressed genes favor +4R is strongly supported, which is consistent across all three stop codons (Table 7).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Functionally important and highly expressed genes such as ribosomal protein genes are expected to evolve strong termination signals.

  • May combine two claims.

    Findingown data

    Both low-CG and high-CG group of genes in human chromosome 1 feature UGA as the most frequent stop codon, whereas human ribosomal protein genes exhibit a strong preference for UAA stop codon.

    “Both low-CG and high-CG group of genes in Chr01 feature UGA as the most frequent stop codon. In contrast, RP genes exhibit a strong preference for UAA stop codon (Table 6).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    It is easier to optimize the AGY subfamily than the UCN subfamily because AGC is clearly preferred over AGU.

    “However, it is easier to optimize the AGY subfamily because AGC is clearly the preferred codon over AGU.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The EMBOSS codon compilation of human genes was done in 1993 and 1994 and did not aim to include only highly expressed genes.

    “The codon compilation of human genes in EMBOSS [33] was done in 1993 and 1994 and did not aim to include only the highly expressed”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [33] Rice, 2000, EMBOSS: The European Molecular Biology Open Software Suite, Trends Genet. source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    Optimization of vaccine mRNA for efficient translation can decrease the copies of vaccine mRNA needed to be carried into host cells.

    “Optimization of vaccine mRNA for efficient translation can decrease the copies of vaccine mRNA needed to be carried into host cells.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Proper optimization of vaccine mRNA can reduce dosage required for each injection leading to more efficient immunization programs.

  • May combine two claims.

    Interpretationreasoning

    The choice of CGG as optimal seemingly resulted from application of both criteria: EMBOSS shows CGG used slightly more frequently than CGC, and CGG seems to have more tRNA decoding it.

    “This choice of CGG as the optimal codon seemingly resulted from application of both criteria above.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Ψ wobbles more in base-pairing than U and can pair not only with A and G, but also, to a lesser extent, with C and U.

    “However, Ψ wobbles more in base-pairing than U and can pair not only with A and G, but also, to a lesser extent, with C and U [16].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [16] Kierzek, 2014, The contribution of pseudouridine to stabilities and structure of RNAs, Nucleic Acids Res. source

      Checked before — its earlier verdict is held back until a new check runs.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    The replacement of uridine by N1-methylpseudourinine (Ψ) complicates some optimization processes because Ψ is more versatile in wobbling than U.

    “The replacement of uridine by N1-methylpseudourinine (Ψ) complicates some of these optimization processes because Ψ is more versatile in wobbling than U.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    For 2-fold Y-ending codons, background mutation favors U-ending codons, but ribosomal protein genes favor C-ending codons, so C-ending codons are optimal.

    “For 2-fold Y-ending codons, the background mutation favors U-ending codons, but ribosomal protein genes favor C-ending codons, so C-ending codon is the optimal codon.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    N1-methylpseudouridines (Ψ) can wobble with all four nucleotides and therefore should not be used in 2-fold codon families.

    “All U nucleotides in the two mRNA vaccines were replaced by N1-methylpseudouridines (Ψ) which can wobble with all for nucleotides and, therefore, should not be used in 2-fold codon families.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: All U nucleotides in the two mRNA vaccines were replaced by N1-methylpseudouridines (Ψ).

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Data for Figure 1 are from three independent quantifications of tissue-specific gene expression represented by three files in the Human Protein Atlas.

    “Data for Figure 1 are from three independent quantifications of tissue-specific gene expression represented by three files in the Human Protein Atlas: proteinatlas.tsv, rna_tissue_gtex.tsv and rna_tissue_fantom.tsv.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Such readthrough events would not only decrease the number of immunogenic proteins, but also produce a longer protein of unknown fate with potentially deleterious effects.

    “Such readthrough events would not only decrease the number of immunogenic proteins, but also produce a longer protein of unknown fate with potentially deleterious effects.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    C-ending codons do not have the Ψ wobble mispairing problem, which is another reason for recoding U-ending codons to C-ending codons.

    “C-ending codons do not have this problem, which serves as another reason for recoding U-ending codons to C-ending codons.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    It is important for vaccine mRNA to be translated accurately because misincorporation of the wrong amino acids would confuse the immune system in target recognition.

    “It is important for vaccine mRNA to be translated accurately because misincorporation of the wrong amino acids would confuse our immune system in target recognition.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    5′-UTRs of highly expressed human genes are almost invariably devoid of upstream AUG that could interfere with translation initiation.

    “One additional advantage of using the 5′-UTR of a highly expressed human gene is that such 5′-UTRs are almost invariably devoid of upstream AUG that could interfere with translation initiation.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    There are three frequently used TRS in coronaviruses.

    “There are three frequently used TRS in coronaviruses (Figure 4D).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    All U nucleotides in the mRNA vaccines have been modified to N1-methyl-pseudouridine (Ψ) to reduce immune reaction towards mRNA and to increase protein production.

    “However, all U nucleotides in the mRNA vaccines have been modified to N1-methyl-pseudouridine (Ψ) [14] to reduce immune reaction towards mRNA and to increase protein production [2,13,58].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [14] European Medicines Agency (2021). Assessment report on Comirnaty (Common Name: COVID-19 mRNA Vaccine) (Nucleoside-Modified) Procedure No. EMEA/H/C/005735/0000, European Medicines Agency.

      Not checked in the free run.

    • cites [2] Corbett, 2020, SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness, Nature source

      Not checked in the free run.

    • cites [13] Weissman, 2015, mRNA transcript therapy, Expert Rev. Vaccines source
    • cites [58] Muramatsu, 2012, Increased erythropoiesis in mice injected with submicrogram quantities of pseudouridine-containing mRNA encoding erythropoietin, Mol. Ther. J. Am. Soc. Gene Ther. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The overuse of AAC by highly expressed E. coli genes could be driven either by selection for increased translation efficiency or increased translation accuracy or both.

    “Therefore, the overuse of AAC by highly expressed E. coli genes could be driven either by selection for increased translation efficiency or increased translation accuracy or both.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Highly expressed E. coli genes use AAC almost exclusively to encode Asn.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    The liberal strategy might lead to more efficient translation elongation if there are too many codons demanding the most abundant tRNA.

    “However, the liberal strategy might lead to more efficient translation elongation if there are too many codons demanding the most abundant tRNA, as I discussed before.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The observed association between poor codon adaptation and variable (functionally unimportant) sites is also consistent with selection for translation efficiency.

    “The observation, however, is also consistent with selection for translation efficiency.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The 5′-UTR secondary structure and codon optimization problems of mRNA-1273 might jointly impact negatively its translation efficiency and contribute to the requirement of a high Moderna vaccine dosage (100 μg/dose) relative to Pfizer/BioNTech (30 μg/dose).

    “These factors might jointly impact negatively the translation efficiency of mRNA-1273 and contribute to the requirement of a high dosage of Moderna vaccine (100 μg/dose) relative to that of Pfizer/BioNTech vaccine (30 μg/dose).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationcitation

    The difference between conserved and variable sites has resulted from selection for accuracy.

    “This is consistent with his inference that the difference between the conserved and variable sites has resulted from selection for accuracy.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37] Akashi, 1994, Synonymous codon usage in Drosophila melanogaster: Natural selection and translational accuracy, Genetics source
    • The authors state this as an assumption: Conserved amino acid sites are functionally important and variable amino acid sites are of limited importance.

  • May combine two claims.

    Premisereasoning

    Alanine is encoded by GCN and glycine by GGN, leading to a high frequency of G at the +4 site.

    “Alanine is encoded by GCN and glycine by GGN, leading to a high frequency of G at the +4 site.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The misreading error rate is six times greater for AAU than for AAC, with the error ratio consistently maintained under Asn-starved and non-starved conditions and with Streptomycin.

    “This misreading error rate is six times greater for AAU than for AAC, with the error ratio consistently maintained in different experimental settings, e.g., under both Asn-starved and non-starved conditions [38], or with Streptomycin used to inhibit translation [39].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [38] Johnston, 1984, Codon specificity of starvation induced misreading, Mol. Gen. Genet. source
    • cites [39] Johnston, 1985, Streptomycin-induced, third-position misreading of the genetic code, J. Mol. Biol. source

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    When an mRNA is not translated efficiently, more of it is needed to produce the same amount of the encoded spike protein.

    “When an mRNA is not translated efficiently, more of it is needed to produce the same amount of the encoded spike protein.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    If the DNA observation can be extrapolated to RNA, G626 would favor purine at the +4 site, i.e., a purine at +4 site is more likely to enhance the stop signal than a pyrimidine.

    “If one may extrapolate this observation from DNA to RNA, then one would predict that G626 would favor purine at the +4 site, i.e., a purine at +4 site is more likely to enhance the stop signal by interacting with G626 in eRF1 than a pyrimidine.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: The observation that glycine interacts more favorably with purine than pyrimidine in protein-DNA interactions can be extrapolated to protein-RNA interactions.

  • May combine two claims.

    Premisecitation

    Both UGAC and UGAU lead to frequent selenocysteine incorporation, suggesting poor decoding of UGA as a stop codon with +4Y.

    “Both UGAC and UGAU lead to frequent selenocysteine incorporation [65], suggesting poor decoding of UGA as a stop codon with +4Y.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [65] McCaughan, 1995, Translational termination efficiency in mammals is influenced by the base following the stop codon, Proc. Natl. Acad. Sci. USA source

      Checked before — its earlier verdict is held back until a new check runs.

  • May combine two claims.

    Interpretationreasoning

    UGA is a poor choice of a stop codon, and UGAU in Pfizer/BioNTech and Moderna mRNA vaccines could be even worse.

    “UGA is a poor choice of a stop codon, and UGAU in Pfizer/BioNTech and Moderna mRNA vaccines could be even worse.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Therefore, the stop signals are ΨGAΨGA instead of UGAUGA in Pfizer/BioNTech's vaccine, and ΨGAΨAAΨAG instead of UGAUAAUAG in Moderna's vaccine.

    “Therefore, the stop signals are ΨGAΨGA instead of UGAUGA in Pfizer/BioNTech’s vaccine, and ΨGAΨAAΨAG instead of UGAUAAUAG in Moderna’s vaccine.”
    Quote in the paperSubstantial claim
55 of 55

  • The paper relies on this without support.

    Proper optimization of vaccine mRNA can reduce dosage required for each injection leading to more efficient immunization programs.

    “Proper optimization of vaccine mRNA can reduce dosage required for each injection leading to more efficient immunization programs.”

  • The authors state this as an assumption.

    The putative sequence of mRNA-1273 is the real mRNA-1273.

    “In this context, it may be safe to assume that the putative sequence is the real mRNA-1273.”

  • The paper relies on this without support.

    The two mRNA vaccines are administered through muscle injection.

    “As the two mRNA vaccines are administered through muscle injection, it is relevant to characterize features of highly expressed muscle genes.”

  • The authors state this as an assumption.

    tRNA abundance is well correlated with tRNA gene copy number.

    “Assuming that tRNA abundance is well correlated with tRNA gene copy number, which is true for Saccharomyces cerevisiae [34] but not known for other eukaryotes”

  • The authors state this as an assumption.

    An injection of Pfizer/BioNTech or Moderna vaccine produces the same number of the encoded spike proteins.

    “one may assume that an injection of Pfizer/BioNTech or Moderna vaccine produces the same number of the encoded spike proteins.”

  • The paper relies on this without support.

    All U nucleotides in the two mRNA vaccines were replaced by N1-methylpseudouridines (Ψ).

    “All U nucleotides in the two mRNA vaccines were replaced by N1-methylpseudouridines (Ψ)”

  • The paper relies on this without support.

    The Pfizer/BioNTech and Moderna vaccines are equivalent in efficacy despite the difference in dosage.

    “Given the difference in dosage (100 μg with mRNA-1273 and 30 μg with BNT-162b2) and the equivalence in efficacy”

  • The paper relies on this without support.

    There is no systematic evaluation of the two codon optimization strategies in translation efficiency.

    “There is no systematic evaluation of these two codon optimization strategies in translation efficiency.”

  • The paper relies on this without support.

    In E. coli, AAC is a major codon for Asn and AAU is a rarely used minor codon.

    “AAC is a major codon (heavily used by highly expressed genes and decoded by the most abundant isoacceptor tRNA {XE “tRNA: isoacceptor”}{XE “isoacceptor tRNA”}) whereas AAU is a rarely used minor codon.”

  • The paper relies on this without support.

    Highly expressed E. coli genes use AAC almost exclusively to encode Asn.

    “Highly expressed E. coli genes use AAC almost exclusively to encode Asn”

  • The authors state this as an assumption.

    Conserved amino acid sites are functionally important and variable amino acid sites are of limited importance.

    “He classified amino acid sites into conserved sites (assumed to be functionally important) and variable sites (assumed to be of limited importance).”

  • The authors state this as an assumption.

    The optimization done by natural selection can be extrapolated to translation in muscle cells.

    “These first two strategies assume that the optimization done by natural selection can be extrapolated to translation in muscle cells.”

  • The paper relies on this without support.

    The 5′-UTR serves two key functions: to stabilize mRNA and to facilitate scanning by the small ribosome subunit to localize the start codon.

    “5′-UTR serves two key functions: to stabilize mRNA and to facilitate scanning by small ribosome subunit to localize the start codon.”

  • The paper relies on this without support.

    G/U base pairs are usually too weak to close a stem.

    “G/U base pairs are usually too weak to close a stem.”

  • The paper relies on this without support.

    Functionally important and highly expressed genes such as ribosomal protein genes are expected to evolve strong termination signals.

    “Functionally important and highly expressed genes such as RP genes are expected to evolve strong termination signals.”

  • The authors state this as an assumption.

    The observation that glycine interacts more favorably with purine than pyrimidine in protein-DNA interactions can be extrapolated to protein-RNA interactions.

    “If one may extrapolate this observation from DNA to RNA, then one would predict that G626 would favor purine at the +4 site, i.e., a purine at +4 site is more likely to enhance the stop signal by interacting with G626 in eRF1 than a pyrimidine.”
16 of 16

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The 5′ UTRs of highly expressed natural genes such as HBA1 and HBB provide high translational activity and mRNA stability.

    “These criteria are met by the 5′ UTRs of highly expressed natural genes such as HBA1 and HBB, encoding α-and β-globin, respectively, which provide high translational activity and mRNA stability [21,22].”

    From Identification of novel 5’ UTR variants for enhanced mRNA translation and vaccine immunogenicity (2026) · cites this paper as [21]

    Section 3.3 identifies the 5′ UTR of the highly expressed α-globin gene as a strategy for facilitating translation. Section 3.5 says α-globin mRNA is translated efficiently and that globin 5′ and 3′ UTRs can confer mRNA stability. It does not specifically establish high translational activity for the HBB 5′ UTR; its discussion of β-globin translation-related design concerns the 3′ UTR. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • The Pfizer-BioNTech mRNA vaccine contains the 5′ UTR of human α-globin and the 3′ UTR AES-mtRNR1 combination.

    “the Pfizer-BioNTech mRNA vaccine contains the 5′ UTR of human α-globin, which was identified as one of the top 20% 5′ UTRs in massive screening studies,10,11,13 and the 3′ UTR AES-mtRNR1 combination of two genes, AES (Amino Enhancer of Split) and mtRNR1 (12S mitochondrial RNA).12”

    From Evaluation of synthetic mRNA with selected UTR sequences and alternative poly(A) tail, in vitro and in vivo (2025) · cites this paper as [13]

  • BioNTech uses a segmented poly(A) tail whose two-tail structures are connected in tandem by a 10 bp UGC linker sequence (A30LA70).

    “For instance, BioNTech uses a segmented poly(A) tail whose two-tail structures are connected in tandem by a 10 bp UGC linker sequence (A30LA70).27,153”

    From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [153]

  • BNT162b2 and mRNA-1273 are composed of 1-methylpseudouridine-modified full-length spike mRNA, with proline substitutions, that is GC rich, codon optimized, and composed of standard mRNA components: cap, 5′ UTR, coding sequence, 3′ UTR, and a poly(A) tail.

    “BNT162b2 (BioNTech/Pfizer) and mRNA-1273 (Moderna) are composed of 1-methylpseudouridine-modified full-length spike mRNA, with proline substitutions, that is GC rich, codon optimized, and composed of standard mRNA components: cap, 5′ UTR, coding sequence, 3′ UTR, and a poly(A) tail.”

    From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [93]

Cites

Flagged first, then by citations

Research works printed but not linked: 3

  1. Xia, X. (2018). Bioinformatics and Translation Elongation. Bioinformatics and the Cell: Modern Computational Approaches in Genomics, Proteomics and Transcriptomics, Springer. · DOI · Paper page
  2. Xia, X. (2018). Bioinformatics and Translation Initiation. Bioinformatics and the Cell: Modern Computational Approaches in Genomics, Proteomics and Transcriptomics, Springer. · DOI · Paper page
  3. Xia, X. (2018). Bioinformatics and Translation Termination in Bacteria. Bioinformatics and the Cell: Modern Computational Approaches in Genomics, Proteomics and Transcriptomics, Springer. · DOI · Paper page

Cited by

Sorted by citations

Related

Authors
Xia, X.
Affiliations
University of Ottawa (CA)
Corresponding author
Xia, Xuhua
ORCID
Xia, Xuhua
Venue
Vaccines
Publisher
MDPI AG
Published
2021-07-03
Volume
9
Issue
7
Pages
734
ISSN
2076-393X (ISSN-L)
DOI
10.3390/vaccines9070734
PMC
PMC8310186
OpenAlex
W3177545102
Cited by
201
References
92
Citations by year
2026: 28 · 2025: 40 · 2024: 42 · 2023: 49 · 2022: 34 · 2021: 8
FWCI
10.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Vaccines (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • uO Research (University of Ottawa) (submittedVersion, cc-by-nd)
  • University of Ottawa - Library
Funders
Natural Sciences and Engineering Research Council of Canada (RGPIN/2018-03878)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
mRNA vaccines, BNT162b2, Moderna vaccine, SARS-CoV-2, 5' untranslated region, codon usage, stop codon, 3' untranslated region, mRNA stability, N1-methylpseudouridine, wobble pairing, translation initiation, vaccine design

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-11-05.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-11-05.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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