Messenger RNA-Based Therapeutics and Vaccines: What’s beyond COVID-19?

Li, Dongqiao; Liu, Cynthia; Li, Yingzhu; Tenchov, Rumiana; Sasso, Janet M.; Zhang, Di; Li, Dan; Zou, Lixue; Wang, Xuezhao; Zhou, Qiongqiong

doi:10.1021/acsptsci.3c00047

Cited by 19 publications

(10 citation statements)

References 86 publications

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“…Given global temperatures rise, melting glaciers releasing old pathogens or the increasing transmission of pathogens from animals to humans, the danger of new diseases emerging is high ( Alempic et al, 2023 ). Therapeutic mRNA molecule has brought new hope, as its production process is quick and easily adjustable for many different therapeutic applications ( Li et al, 2023 ; Yu et al, 2023 ). By changing the sequence, any protein of therapeutic interest can be obtained.…”

Section: Discussionmentioning

confidence: 99%

The potential of N2-modified cap analogues for precise genetic manipulation through mRNA engineering

Kurpiejewski,

Stankiewicz-Drogon,

Piecyk

et al. 2024

Front. Mol. Biosci.

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The technology of mRNA-based drugs is currently being intensively developed and implemented. Medical products of this type are already being used as viral vaccines and could potentially find application in a wide range of diseases. The tremendous interest in mRNA is due to the relatively easy production process, which can be quickly adapted to meet societal needs. The properties of this molecule depend on the structure of its individual components, such as the structure of the cap at the 5ʹ end. Modifications of the cap significantly affect the translational potential and lifespan of the whole mRNA. In the current work, we present the synthesis of derivatives of cap analogues modified at the N2 position of 7-methylguanosine. In addition to the substituent at the N2 position, the derivatives had either an extended triphosphate chain, a thiophosphate modification, an added cap1-modified nucleotide or an extended linker between the substituent and 7-methylguanosine. The compounds were tested for use as translation inhibitors and as components for mRNA preparation and appeared of interest for both applications.

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Section: Discussionmentioning

confidence: 99%

The potential of N2-modified cap analogues for precise genetic manipulation through mRNA engineering

Kurpiejewski,

Stankiewicz-Drogon,

Piecyk

et al. 2024

Front. Mol. Biosci.

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“…Persistent circulating SARS-CoV-2 Spike was recently proposed to be causative of the COVID-19 associated syndrome termed PASC (post-acute sequelae of COVID-19) [25,26]. Considering that the anti-SARS vaccination campaigns are expected to be still ongoing for the next coming years [5], extensive analysis of SARS-CoV-2 Spike in ex vivo cellular systems is required for understanding possible impacts on vaccination [7–9].…”

Section: Discussionmentioning

confidence: 99%

The anti-SARS-CoV-2 BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation and expression of embryo-fetal globin genes in human erythroleukemia K562 cells

Zurlo,

Gasparello,

Verona

et al. 2023

Preprint

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The COVID-19 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the ongoing coronavirus disease 2019 (COVID-19) pandemic. The SARS-CoV-2 Spike protein (S-protein) plays an important role in the early phase of SARS-CoV2 infection through efficient interaction with ACE2. The S-protein is produced by RNA-based COVID-19 vaccines, and has been hypothesized to be responsible for damaging cells of several tissues and for some important side effects of RNA-based COVID-19 vaccines. The aim of this study was to verify the effect of the BNT162b2 vaccine on erythroid differentiation of the human K562 cell line, that has been in the past intensively studied as a model system mimicking some steps of erythropoiesis. We found that the BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation of K562 cells. Reverse-transcription-PCR and Western blotting assays demonstrated that suppression of erythroid differentiation was associated with sharp inhibition of the expression of α-globin and γ-globin mRNA accumulation. Inhibition of accumulation of ζ-globin and ε-globin mRNAs was also observed. In addition, we provide in silico studies suggesting a direct interaction between SARS-CoV-2 Spike protein and Hb Portland, that is the major hemoglobin produced by K562 cells. This study thus provides information suggesting the need of great attention on possible alteration of hematopoietic parameters following SARS-CoV-2 infection and/or COVID-19 vaccination.

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“…It must be kept in mind that vaccines’ immunogenicity (including those against COVID-19) is affected by various factors. It was shown that the following factors might contribute to different vaccine responses in different regions: (i) age—infants do not have a mature immune system and therefore their cell-mediated immune responses are very weak, aging may lead to immune-depression and inflammations and a high prevalence of comorbidities, and in aged patients, immunogenicity is lower; (ii) poor diet and malnutrition and composition of gut microflora—immune responses to vaccination is weaker in low- and middle-income countries in comparison to high-income ones; (iii) it was shown that humoral responses after vaccination against COVID-19 were weaker in obese people; (iv) immunogenicity also varies between males and females (women usually have higher immune responses), which can lead to differences in responses to vaccine; and (v) some studies suggest that host genetics also may contribute to vaccination outcomes [ 89 ]. Table 3 shows a comparison of inactivated vaccines’ efficacy as an example.…”

Section: Perspectives and Conclusionmentioning

confidence: 99%

COVID-19 Vaccines over Three Years after the Outbreak of the COVID-19 Epidemic

Zasada,

Darlińska,

Wiatrzyk

et al. 2023

Viruses

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The outbreak of COVID-19 started in December 2019 and spread rapidly all over the world. It became clear that the development of an effective vaccine was the only way to stop the pandemic. It was the first time in the history of infectious diseases that the process of the development of a new vaccine was conducted on such a large scale and accelerated so rapidly. At the end of 2020, the first COVID-19 vaccines were approved for marketing. At the end of March 2023, over three years after the outbreak of the COVID-19 pandemic, 199 vaccines were in pre-clinical development and 183 in clinical development. The candidate vaccines in the clinical phase are based on the following platforms: protein subunit, DNA, RNA, non-replication viral vector, replicating viral vector, inactivated virus, virus-like particles, live attenuated virus, replicating viral vector combined with an antigen-presenting cell, non-replication viral vector combined with an antigen-presenting cell, and bacterial antigen-spore expression vector. Some of the new vaccine platforms have been approved for the first time for human application. This review presents COVID-19 vaccines currently available in the world, procedures for assurance of the quality and safety of the vaccines, the vaccinated population, as well as future perspectives for the new vaccine platforms in drug and therapy development for infectious and non-infectious diseases.

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Messenger RNA-Based Therapeutics and Vaccines: What’s beyond COVID-19?

Cited by 19 publications

References 86 publications

The potential of N2-modified cap analogues for precise genetic manipulation through mRNA engineering

The potential of N2-modified cap analogues for precise genetic manipulation through mRNA engineering

The anti-SARS-CoV-2 BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation and expression of embryo-fetal globin genes in human erythroleukemia K562 cells

COVID-19 Vaccines over Three Years after the Outbreak of the COVID-19 Epidemic

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