Publisher Correction: Evolution of the market for mRNA technology

In recent years, vaccine development using ribonucleic acid (RNA) has become the most promising and studied approach to produce safe and effective new vaccines, not only for prophylaxis but also as a treatment. The use of messenger RNA (mRNA) as an immunogenic has several advantages to vaccine development compared to other platforms, such as lower coast, the absence of cell cultures, and the possibility to combine different targets. During the COVID-19 pandemic, the use of mRNA as a vaccine became more relevant; two out of the four most widely applied vaccines against COVID-19 in the world are based on this platform. However, even though it presents advantages for vaccine application, mRNA technology faces several pivotal challenges to improve mRNA stability, delivery, and the potential to generate the related protein needed to induce a humoral- and T-cell-mediated immune response. The application of mRNA to vaccine development emerged as a powerful tool to fight against cancer and non-infectious and infectious diseases, for example, and represents a relevant research field for future decades. Based on these advantages, this review emphasizes mRNA and self-amplifying RNA (saRNA) for vaccine development, mainly to fight against COVID-19, together with the challenges related to this approach.

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mRNA technology may treat stubborn diseases

The New Scientist ◽

10.1016/s0262-4079(21)02292-2 ◽

2022 ◽

Vol 253 (3367) ◽

pp. 9

Author(s):

Michael Le Page

Keyword(s):

Mrna Technology

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Systematic identification of factors in zebrafish regulating the early midbrain and cerebellar development by odered differential display and caged mRNA technology

Frontiers in Bioscience ◽

10.2741/1205 ◽

2004 ◽

Vol 9 (1-3) ◽

pp. 93 ◽

Cited By ~ 7

Author(s):

Hitoshi Okamoto

Keyword(s):

Differential Display ◽

Cerebellar Development ◽

Mrna Technology ◽

Systematic Identification

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Dual mRNA therapy restores metabolic function in long-term studies in mice with propionic acidemia

Nature Communications ◽

10.1038/s41467-020-19156-3 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Lei Jiang ◽

Ji-Sun Park ◽

Ling Yin ◽

Rodrigo Laureano ◽

Eric Jacquinet ◽

...

Keyword(s):

Genetic Disorders ◽

Propionic Acidemia ◽

Repeat Dose ◽

Dependent Manner ◽

Messenger Rnas ◽

Enzyme Replacement ◽

Life Threatening ◽

Mrna Technology ◽

Dose Dependent

Abstract Propionic acidemia/aciduria (PA) is an ultra-rare, life-threatening, inherited metabolic disorder caused by deficiency of the mitochondrial enzyme, propionyl-CoA carboxylase (PCC) composed of six alpha (PCCA) and six beta (PCCB) subunits. We herein report an enzyme replacement approach to treat PA using a combination of two messenger RNAs (mRNAs) (dual mRNAs) encoding both human PCCA (hPCCA) and PCCB (hPCCB) encapsulated in biodegradable lipid nanoparticles (LNPs) to produce functional PCC enzyme in liver. In patient fibroblasts, dual mRNAs encoded proteins localize in mitochondria and produce higher PCC enzyme activity vs. single (PCCA or PCCB) mRNA alone. In a hypomorphic murine model of PA, dual mRNAs normalize ammonia similarly to carglumic acid, a drug approved in Europe for the treatment of hyperammonemia due to PA. Dual mRNAs additionally restore functional PCC enzyme in liver and thus reduce primary disease-associated toxins in a dose-dependent manner in long-term 3- and 6-month repeat-dose studies in PA mice. Dual mRNAs are well-tolerated in these studies with no adverse findings. These studies demonstrate the potential of mRNA technology to chronically administer multiple mRNAs to produce large complex enzymes, with applicability to other genetic disorders.

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Lipid Nanoparticles for Organ-Specific mRNA Therapeutic Delivery

Pharmaceutics ◽

10.3390/pharmaceutics13101675 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1675

Author(s):

Magdalena M. Żak ◽

Lior Zangi

Keyword(s):

Lipid Nanoparticles ◽

Target Cells ◽

Therapeutic Delivery ◽

The Past ◽

Recent Success ◽

Organ Specific ◽

Mrna Therapeutics ◽

Mrna Technology ◽

Specific Mrna

Advances in the using in vitro transcribed (IVT) modRNA in the past two decades, especially the tremendous recent success of mRNA vaccines against SARS-CoV-2, have brought increased attention to IVT mRNA technology. Despite its well-known use in infectious disease vaccines, IVT modRNA technology is being investigated mainly in cancer immunotherapy and protein replacement therapy, with ongoing clinical trials in both areas. One of the main barriers to progressing mRNA therapeutics to the clinic is determining how to deliver mRNA to target cells and protect it from degradation. Over the years, many different vehicles have been developed to tackle this issue. Desirable vehicles must be safe, stable and preferably organ specific for successful mRNA delivery to clinically relevant cells and tissues. In this review we discuss various mRNA delivery platforms, with particular focus on attempts to create organ-specific vehicles for therapeutic mRNA delivery.

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COVID-19 vaccination intention and vaccine characteristics influencing vaccination acceptance: a global survey of 17 countries

Infectious Diseases of Poverty ◽

10.1186/s40249-021-00900-w ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Li Ping Wong ◽

Haridah Alias ◽

Mahmoud Danaee ◽

Jamil Ahmed ◽

Abhishek Lachyan ◽

...

Keyword(s):

Adverse Reactions ◽

Local Population ◽

Herd Immunity ◽

Vaccine Hesitancy ◽

Multivariable Logistic Regression Analysis ◽

Individual Country ◽

Vaccine Acceptance ◽

Vaccination Acceptance ◽

Mrna Technology ◽

To Receive

Abstract Background The availability of various types of COVID-19 vaccines and diverse characteristics of the vaccines present a dilemma in vaccination choices, which may result in individuals refusing a particular COVID-19 vaccine offered, hence presenting a threat to immunisation coverage and reaching herd immunity. The study aimed to assess global COVID-19 vaccination intention, vaccine characteristics influencing vaccination acceptance and desirable vaccine characteristics influencing the choice of vaccines. Methods An anonymous cross-sectional survey was conducted between 4 January and 5 March 2021 in 17 countries worldwide. Proportions and the corresponding 95% confidence intervals (CI) of COVID-19 vaccine acceptance and vaccine characteristics influencing vaccination acceptance were generated and compared across countries and regions. Multivariable logistic regression analysis was used to determine the factors associated with COVID-19 vaccine hesitancy. Results Of the 19,714 responses received, 90.4% (95% CI 81.8–95.3) reported likely or extremely likely to receive COVID-19 vaccine. A high proportion of likely or extremely likely to receive the COVID-19 vaccine was reported in Australia (96.4%), China (95.3%) and Norway (95.3%), while a high proportion reported being unlikely or extremely unlikely to receive the vaccine in Japan (34.6%), the U.S. (29.4%) and Iran (27.9%). Males, those with a lower educational level and those of older age expressed a higher level of COVID-19 vaccine hesitancy. Less than two-thirds (59.7%; 95% CI 58.4–61.0) reported only being willing to accept a vaccine with an effectiveness of more than 90%, and 74.5% (95% CI 73.4–75.5) said they would accept a COVID-19 vaccine with minor adverse reactions. A total of 21.0% (95% CI 20.0–22.0) reported not accepting an mRNA vaccine and 51.8% (95% CI 50.3–53.1) reported that they would only accept a COVID-19 vaccine from a specific country‐of‐origin. Countries from the Southeast Asia region reported the highest proportion of not accepting mRNA technology. The highest proportion from Europe and the Americas would only accept a vaccine produced by certain countries. The foremost important vaccine characteristic influencing vaccine choice is adverse reactions (40.6%; 95% CI 39.3–41.9) of a vaccine and effectiveness threshold (35.1%; 95% CI 33.9–36.4). Conclusions The inter-regional and individual country disparities in COVID-19 vaccine hesitancy highlight the importance of designing an efficient plan for the delivery of interventions dynamically tailored to the local population. Graphic Abstract

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Thrombosis and COVID-19 vaccines

REVISTA CIÊNCIAS EM SAÚDE ◽

10.21876/rcshci.v11i2.1165 ◽

2021 ◽

Vol 11 (2) ◽

pp. 1-2

Author(s):

Melissa Andreia De Moraes Silva ◽

Mateus Alves Borges Cristino ◽

Ricardo Jayme Procópio

Keyword(s):

United States ◽

Adverse Reactions ◽

Adenovirus Vector ◽

The United States ◽

Venous Sinus ◽

Mrna Technology

Vaccines against COVID-19 from Moderna Biotech Spain, SL (COVID-19 Vaccine Moderna – mRNA technology), AstraZeneca (Oxford/Astrazeneca Vaccine - ChAdOx1 - adenovirus vector technology) and Janssen-Cilag International NV (COVID-19 Vaccine) Janssen - Ad.26.COV2.S - adenovirus vector technology) used in Europe, the United States and Brazil has presented severe thrombotic adverse reactions. The recorded thrombosis occurred in unusual sites, such as the sagittal venous sinus.

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Effects of Age, Sex, Serostatus and Underlying Comorbidities on Humoral Response Post-SARS-CoV-2 Pfizer-BioNTech Vaccination: A Systematic Review

10.1101/2021.10.10.21264825 ◽

2021 ◽

Author(s):

Kin Israel Notarte ◽

Abbygail Therese Ver ◽

Jacqueline Veronica Velasco ◽

Adriel Pastrana ◽

Jesus Alfonso Catahay ◽

...

Keyword(s):

Immune Response ◽

Humoral Response ◽

Older Individuals ◽

Response Mechanism ◽

Humoral Immune ◽

Different Populations ◽

Male Sex ◽

Mrna Technology ◽

Antibody Levels ◽

Response Post

With the advent of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, several vaccines have been developed to mitigate its spread and prevent adverse consequences of the Coronavirus Disease 2019 (COVID-19). The mRNA technology is an unprecedented vaccine, usually given in two doses to prevent SARS-CoV-2 infections. Despite effectiveness and safety, inter-individual immune response heterogeneity has been observed in recipients of mRNA-based vaccines. As a novel disease, the specific immune response mechanism responsible for warding off COVID-19 remains unclear at this point. However, significant evidence suggests that humoral response plays a crucial role in affording immunoprotection and preventing debilitating sequelae from COVID-19. As such this paper focused on the possible effects of age, sex, serostatus, and comorbidities on humoral response (i.e., total antibodies, IgG and/or IgA) of different populations post-mRNA-based Pfizer-BioNTech vaccination. A systematic search of literature was performed through PubMed, Cochrane CENTRAL, and Google Scholar. Studies were included if they reported humoral response to COVID-19 mRNA vaccines. A total of 32 studies was identified and reviewed, and the percent difference of means of reported antibody levels were calculated for comparison. Findings revealed that older individuals, the male sex, seronegativity, and those with more comorbidities mounted less humoral immune response. Given these findings, several recommendations were proposed regarding the current vaccination practices. These include giving additional doses of vaccination for immunocompromised and elderly populations. Another recommendation is conducting clinical trials in giving a combined scheme of mRNA vaccines, protein vaccines, and vector-based vaccines.

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