The future in an RNA molecule: from mRNA vaccines to therapeutics – An interview with Drew Weissman

Ruffell, Daniela

doi:10.1002/1873-3468.14190

Cited by 6 publications

(7 citation statements)

References 11 publications

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“…Unmodified mRNA is being used in non-COVID-19 clinical trials, particularly for developing new cancer treatments. It has been suggested that the challenge associated with the activation of an immune response against cancer cells could be better surmounted with the use of unmodified mRNA (with its stronger adjuvant activity) coding for proteins usually present in cancer cells but not in healthy cells, in order to turn a cold tumor into a hot tumor more effectively ( Ruffell, 2021 ). In fact, BioNTech just announced the use of unmodified mRNA encapsulated in a lipoplex delivery formulation, following this concept, for treatment of colorectal cancer patients in phase two trials ( BioNTech, 2021 ).…”

Section: Modified Vs Unmodified Covid-19 Mrna Vaccines Lead To Different Outcomesmentioning

confidence: 99%

“…It is believed that, while muscle cells are not very efficient in the translation of the mRNA encoding the Spike protein, LNPs ultimately carry their cargo to the lymph nodes and are internalized by dendritic cells. The Spike protein is synthesized in these cells from the mRNA template and displayed to other immune system cells (T and B cells) to trigger the immune response ( Ruffell, 2021 ). Without LNPs formulations, the success of mRNA vaccines would not have been possible.…”

Section: Introductionmentioning

confidence: 99%

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The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines

Morais

Adachi

2021

Front. Cell Dev. Biol.

138

112

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The current COVID-19 pandemic is a massive source of global disruption, having led so far to two hundred and fifty million COVID-19 cases and almost five million deaths worldwide. It was recognized in the beginning that only an effective vaccine could lead to a way out of the pandemic, and therefore the race for the COVID-19 vaccine started immediately, boosted by the availability of the viral sequence data. Two novel vaccine platforms, based on mRNA technology, were developed in 2020 by Pfizer-BioNTech and Moderna Therapeutics (comirnaty® and spikevax®, respectively), and were the first ones presenting efficacies higher than 90%. Both consisted of N1-methyl-pseudouridine-modified mRNA encoding the SARS-COVID-19 Spike protein and were delivered with a lipid nanoparticle (LNP) formulation. Because the delivery problem of ribonucleic acids had been known for decades, the success of LNPs was quickly hailed by many as the unsung hero of COVID-19 mRNA vaccines. However, the clinical trial efficacy results of the Curevac mRNA vaccine (CVnCoV) suggested that the delivery system was not the only key to the success. CVnCoV consisted of an unmodified mRNA (encoding the same spike protein as Moderna and Pfizer-BioNTech’s mRNA vaccines) and was formulated with the same LNP as Pfizer-BioNTech’s vaccine (Acuitas ALC-0315). However, its efficacy was only 48%. This striking difference in efficacy could be attributed to the presence of a critical RNA modification (N1-methyl-pseudouridine) in the Pfizer-BioNTech and Moderna’s mRNA vaccines (but not in CVnCoV). Here we highlight the features of N1-methyl-pseudouridine and its contributions to mRNA vaccines.

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Section: Modified Vs Unmodified Covid-19 Mrna Vaccines Lead To Different Outcomesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines

Morais

Adachi

2021

Front. Cell Dev. Biol.

138

112

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“…Remarkably, mRNA-1273 from Moderna began its first US clinical trial just 66 days after the SARS-CoV-2 sequence was made available. These two products are the first RNA vaccines approved for clinical use and have clearly demonstrated that RNA-based vaccines offer several major competitive advantages and potential applications [ 27 ].…”

Section: Prevention For Covid-19mentioning

confidence: 99%

A critical overview of current progress for COVID-19: development of vaccines, antiviral drugs, and therapeutic antibodies

Kumari

et al. 2022

J Biomed Sci

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The novel coronavirus disease (COVID-19) pandemic remains a global public health crisis, presenting a broad range of challenges. To help address some of the main problems, the scientific community has designed vaccines, diagnostic tools and therapeutics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The rapid pace of technology development, especially with regard to vaccines, represents a stunning and historic scientific achievement. Nevertheless, many challenges remain to be overcome, such as improving vaccine and drug treatment efficacies for emergent mutant strains of SARS-CoV-2. Outbreaks of more infectious variants continue to diminish the utility of available vaccines and drugs. Thus, the effectiveness of vaccines and drugs against the most current variants is a primary consideration in the continual analyses of clinical data that supports updated regulatory decisions. The first two vaccines granted Emergency Use Authorizations (EUAs), BNT162b2 and mRNA-1273, still show more than 60% protection efficacy against the most widespread current SARS-CoV-2 variant, Omicron. This variant carries more than 30 mutations in the spike protein, which has largely abrogated the neutralizing effects of therapeutic antibodies. Fortunately, some neutralizing antibodies and antiviral COVID-19 drugs treatments have shown continued clinical benefits. In this review, we provide a framework for understanding the ongoing development efforts for different types of vaccines and therapeutics, including small molecule and antibody drugs. The ripple effects of newly emergent variants, including updates to vaccines and drug repurposing efforts, are summarized. In addition, we summarize the clinical trials supporting the development and distribution of vaccines, small molecule drugs, and therapeutic antibodies with broad-spectrum activity against SARS-CoV-2 strains.

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“… 126 With the involvement of numerous pharma companies, we could also expect that these processes could fasten up and will be available to the public very soon. 127 …”

Section: Challengesmentioning

confidence: 99%