“…Moreover, owing to their relatively small size (~100 nm), neutral surface charge and diffusible PEG lipid coating, mRNA LNPs might also enter the lymphatics to directly target LN-resident APCs and B cells [ 11 , 58 ]. Finally, although these cells are often overlooked in flow cytometry studies, it is very likely that cell types such as myocytes, epithelial cells and fibroblasts also contribute to local mRNA expression [ 59 ]. Fig.…”
Section: Covid-19 Mrna Vaccines: Differences and Similaritiesmentioning
In less than one year since the outbreak of the COVID-19 pandemic, two mRNA-based vaccines, BNT162b2 and mRNA-1273, were granted the first historic authorization for emergency use, while another mRNA vaccine, CVnCoV, progressed to phase 3 clinical testing. The COVID-19 mRNA vaccines represent a new class of vaccine products, which consist of synthetic mRNA strands encoding the SARS-CoV-2 Spike glycoprotein, packaged in lipid nanoparticles to deliver mRNA to cells. This review digs deeper into the scientific breakthroughs of the last decades that laid the foundations for the rapid rise of mRNA vaccines during the COVID-19 pandemic. As well as providing momentum for mRNA vaccines, SARS-CoV-2 represents an ideal case study allowing to compare design-activity differences between the different mRNA vaccine candidates. Therefore, a detailed overview of the composition and (pre)clinical performance of the three most advanced mRNA vaccines is provided and the influence of choices in their structural design on to their immunogenicity and reactogenicity profile is discussed in depth. In addition to the new fundamental insights in the mRNA vaccines' mode of action highlighted here, we also point out which unknowns remain that require further investigation and possibly, optimization in future mRNA vaccine development.
“…Moreover, owing to their relatively small size (~100 nm), neutral surface charge and diffusible PEG lipid coating, mRNA LNPs might also enter the lymphatics to directly target LN-resident APCs and B cells [ 11 , 58 ]. Finally, although these cells are often overlooked in flow cytometry studies, it is very likely that cell types such as myocytes, epithelial cells and fibroblasts also contribute to local mRNA expression [ 59 ]. Fig.…”
Section: Covid-19 Mrna Vaccines: Differences and Similaritiesmentioning
In less than one year since the outbreak of the COVID-19 pandemic, two mRNA-based vaccines, BNT162b2 and mRNA-1273, were granted the first historic authorization for emergency use, while another mRNA vaccine, CVnCoV, progressed to phase 3 clinical testing. The COVID-19 mRNA vaccines represent a new class of vaccine products, which consist of synthetic mRNA strands encoding the SARS-CoV-2 Spike glycoprotein, packaged in lipid nanoparticles to deliver mRNA to cells. This review digs deeper into the scientific breakthroughs of the last decades that laid the foundations for the rapid rise of mRNA vaccines during the COVID-19 pandemic. As well as providing momentum for mRNA vaccines, SARS-CoV-2 represents an ideal case study allowing to compare design-activity differences between the different mRNA vaccine candidates. Therefore, a detailed overview of the composition and (pre)clinical performance of the three most advanced mRNA vaccines is provided and the influence of choices in their structural design on to their immunogenicity and reactogenicity profile is discussed in depth. In addition to the new fundamental insights in the mRNA vaccines' mode of action highlighted here, we also point out which unknowns remain that require further investigation and possibly, optimization in future mRNA vaccine development.
“…Concerning viral infections (i.e., syncytial virus in respiratory tract) it provides tRNA cleavage increasing small tiRNA fragments that are essential for viral replication (Wang et al, 2013). Although LNPs-based mRNA delivery system seems to be more sophisticated and effectivecompared to polymers or oil-in-water emulsions-are depended on temperature limitations (Blakney et al, 2020). This is an important and challenging parameter.…”
Coronavirus-related Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) initially was detected in Wuhan, Hubei, China. Since early 2021, World Health Organization (WHO) has declared Coronavirus Disease 2019 (COVID-19) a pandemic due to rapidly transformed to a globally massive catastrophic viral infection. In order to confront this emergency situation, many pharmaceutical companies focused on the design and development of efficient vaccines that are considered necessary for providing a level of normalization in totally affected human social-economical activity worldwide. A variety of vaccine types are under development, validation or even some of them have already completed these stages, initially approved as conditional marketing authorisation by Food and Drug Administration (FDA), European Medicines Agency (EMA), and other national health authorities for commercial purposes (in vivo use in general population), accelerating their production and distribution process. Innovative nucleoside-modified viral messenger RNA (v-mRNA)—based vaccines encapsulated within nanoparticles—specifically lipid ones (LNPs)—are now well recognized. Although this is a promising genetic engineering topic in the field of nanopharmacogenomics or targeted nucleic vaccines, there are limited but continuously enriched in vivo data in depth of time regarding their safety, efficacy, and immune response. In the current paper we expand the limited published data in the field of ribosome machinery and SARS-CoV-2 mRNA fragment vaccines interaction by describing their functional specialization and modifications. Additionally, alterations in post-transcriptional/translational molecules and mechanisms that could potentially affect the interaction between target cells and vaccines are also presented. Understanding these mechanisms is a crucial step for the next generation v-mRNA vaccines development.
“…(2017)). Furthermore, using nanoparticle delivery of mRNA to adipocytes, via subcutaneous injection, is a very promising next-generation approach for protein replacement therapies and vaccination (Blakney et al . (2020)).…”
Fluorescence microscopy, which visualizes cellular components with fluorescent stains, is an invaluable method in image cytometry. From these images various cellular features can be extracted. Together these features form phenotypes that can be used to determine effective drug therapies, such as those based on nanomedicines. Unfortunately, fluorescence microscopy is time-consuming, expensive, labour intensive, and toxic to the cells. Bright-field images lack these downsides but also lack the clear contrast of the cellular components and hence are difficult to use for downstream analysis. Generating the fluorescence images directly from bright-field images would get the best of both worlds, but can be very challenging to do for poorly visible cellular structures in the bright-field images. To tackle this problem deep learning models were explored to learn the mapping between bright-field and fluorescence images to enable virtual staining for adipocyte cell images. The models were tailored for each imaging channel, paying particular attention to the various challenges in each case, and those with the highest fidelity in extracted cell-level features were selected. The solutions included utilizing privileged information for the nuclear channel, and using image gradient information and adversarial training for the lipids channel. The former resulted in better morphological and count features and the latter resulted in more faithfully captured defects in the lipids, which are key features required for downstream analysis of these channels.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
