The mRNA-LNP vaccines – the good, the bad and the ugly?

Igyártó, Botond Z.; Qin, Zhen

doi:10.3389/fimmu.2024.1336906

Cited by 2 publications

(1 citation statement)

References 146 publications

(156 reference statements)

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“…In this case, methods should be used to increase the immunogenicity of the drug. It should be noted that in the development of mRNA vaccines, an excessive overreaction of the immune system is undesirable due to possible damage to the human organism ( Igyártó and Qin, 2024 ) and should be taken into account during codon optimization. On the other hand, if a transgene introduced into the organism is intended to lead to the production of the corresponding protein, any degree of immunogenicity will reduce the effectiveness of the therapy.…”

Section: The Effect Of Codon Optimization On Immunogenicitymentioning

confidence: 99%

Codon-optimization in gene therapy: promises, prospects and challenges

Paremskaia,

Kogan,

Murashkina

et al. 2024

Front. Bioeng. Biotechnol.

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Codon optimization has evolved to enhance protein expression efficiency by exploiting the genetic code’s redundancy, allowing for multiple codon options for a single amino acid. Initially observed in E. coli, optimal codon usage correlates with high gene expression, which has propelled applications expanding from basic research to biopharmaceuticals and vaccine development. The method is especially valuable for adjusting immune responses in gene therapies and has the potenial to create tissue-specific therapies. However, challenges persist, such as the risk of unintended effects on protein function and the complexity of evaluating optimization effectiveness. Despite these issues, codon optimization is crucial in advancing gene therapeutics. This study provides a comprehensive review of the current metrics for codon-optimization, and its practical usage in research and clinical applications, in the context of gene therapy.

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Section: The Effect Of Codon Optimization On Immunogenicitymentioning

confidence: 99%

Codon-optimization in gene therapy: promises, prospects and challenges

Paremskaia,

Kogan,

Murashkina

et al. 2024

Front. Bioeng. Biotechnol.

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Reports of Batch-Dependent Suspected Adverse Events of the BNT162b2 mRNA COVID-19 Vaccine: Comparison of Results from Denmark and Sweden

Manniche,

Schmeling,

Gilthorpe

et al. 2024

Medicina

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Background and Objective: An unexpected batch-dependent safety signal for the BNT162b2 mRNA COVID-19 vaccine was recently identified in a nationwide study from Denmark, but the generalizability of this finding is unknown. Therefore, we compared batch-dependent rates of suspected adverse events (SAEs) reported to national authorities in Denmark and Sweden. Materials and Methods: SAE and vaccine batch data were received from national authorities in Denmark and Sweden, and analyses of heterogeneity in the relationship between numbers of vaccine doses and SAEs per batch were performed, along with comparison of SAE rates and severities for batches that were shared between the two countries. Results: Significant batch-dependent heterogeneity was found in the number of SAEs per 1000 doses for both countries, with batches associated with high SAE rates detected in the early phase of the vaccination campaign and positive correlations observed between the two countries for the severity of SAEs from vaccine batches that they shared. Mild SAEs predominated in the batches used in the early part of the vaccination roll-out, where markedly higher SAE rates per 1000 doses in Denmark for the batches that were shared between the two countries suggested that a large proportion of these SAEs were under-reported in Sweden. Conclusions: The batch-dependent safety signal observed in Denmark and now confirmed in Sweden suggests that early commercial batches of BNT162b2 may have differed from those used later on, and these preliminary and hypothesis-generating results warrant further study.

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The mRNA-LNP vaccines – the good, the bad and the ugly?

Cited by 2 publications

References 146 publications

Codon-optimization in gene therapy: promises, prospects and challenges

Codon-optimization in gene therapy: promises, prospects and challenges

Reports of Batch-Dependent Suspected Adverse Events of the BNT162b2 mRNA COVID-19 Vaccine: Comparison of Results from Denmark and Sweden

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