scholarly journals Next-Generation Vaccines Based on Self-Amplifying RNA

2021 ◽  
Author(s):  
Fatemeh Nafian ◽  
Simin Nafian ◽  
Ghazal Soleymani ◽  
Zahra Pourmanouchehri ◽  
Mahnaz Kiyanjam ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Rna Viruses ◽  
Host Cells ◽  
Live Vaccines ◽  
Stable Integration ◽  
Individual Host ◽  
Transfer Genes ◽  
Cell Genome ◽  
Synthetic Mrna ◽  
Rna And Dna

Recently, nucleic acid-based RNA and DNA vaccines have represented a better solution to avoid infectious diseases than “traditional” live and non-live vaccines. Synthetic RNA and DNA molecules allow scalable, rapid, and cell-free production of vaccines in response to an emerging disease such as the current COVID-19 pandemic. The development process begins with laboratory transcription of sequences encoding antigens, which are then formulated for delivery. The various potent of RNA over live and inactivated viruses are proven by advances in delivery approaches. These vaccines contain no infectious elements nor the risk of stable integration with the host cell genome compared to conventional vaccines. Conventional mRNA-based vaccines transfer genes of interest (GOI) of attenuated mRNA viruses to individual host cells. Synthetic mRNA in liposomes forms a modern, refined sample, resulting in a safer version of live attenuated RNA viruses. Self-amplifying RNA (saRNA) is a replicating version of mRNA-based vaccines that encode both (GOI) and viral replication machinery. saRNA is required at lower doses than conventional mRNA, which may improve immunization. Here we provide an overview of current mRNA vaccine approaches, summarize highlight challenges and recent successes, and offer perspectives on the future of mRNA vaccines.

scholarly journals Intercellular Transmission of Naked Viruses through Extracellular Vesicles: Focus on Polyomaviruses

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1086
Author(s):  
Francois Helle ◽  
Lynda Handala ◽  
Marine Bentz ◽  
Gilles Duverlie ◽  
Etienne Brochot
Keyword(s):  
Immune System ◽  
Extracellular Vesicles ◽  
Rna Viruses ◽  
Viral Transmission ◽  
Viral Fitness ◽  
Host Cells ◽  
Dna Viruses ◽  
Recent Advances ◽  
Viral Particles ◽  
Similar Strategy

Extracellular vesicles have recently emerged as a novel mode of viral transmission exploited by naked viruses to exit host cells through a nonlytic pathway. Extracellular vesicles can allow multiple viral particles to collectively traffic in and out of cells, thus enhancing the viral fitness and diversifying the transmission routes while evading the immune system. This has been shown for several RNA viruses that belong to the Picornaviridae, Hepeviridae, Reoviridae, and Caliciviridae families; however, recent studies also demonstrated that the BK and JC viruses, two DNA viruses that belong to the Polyomaviridae family, use a similar strategy. In this review, we provide an update on recent advances in understanding the mechanisms used by naked viruses to hijack extracellular vesicles, and we discuss the implications for the biology of polyomaviruses.

scholarly journals Composition of Pseudomonas aeruginosa slime

1969 ◽  
Vol 112 (4) ◽  
pp. 521-525 ◽  
Author(s):  
M. R. W. Brown ◽  
J. H. Scott Foster ◽  
J. R. Clamp
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Hyaluronic Acid ◽  
Nucleic Acid ◽  
Growth Medium ◽  
Extraction Procedure ◽  
The Other ◽  
Minor Components ◽  
Polysaccharide Fraction ◽  
Defined Media ◽  
Rna And Dna

1. The slime produced by eight strains of Pseudomonas aeruginosa on a number of different media was demonstrated to be qualitatively the same. Small quantitative differences may be occasioned by differences in the extraction procedure, the growth medium or the strain of organism used. 2. The slime was shown to be predominantly polysaccharide with some nucleic acid material and a small amount of protein. 3. The hydrolysed polysaccharide fraction consists mainly of glucose with smaller amounts of mannose. This accounts for some 50–60% of the total slime. In addition, there is some 5% of hyaluronic acid. The nucleic acid material represents approx. 20% of the total weight, and is composed of both RNA and DNA. 4. Minor components are protein, rhamnose and glucosamine, the protein being less than 5% of the total. 5. Hyaluronic acid is produced in greater quantities from nutrient broth than from chemically defined media, and is more firmly attached to the cells than the other components.

Tumor cell metabolism in vitro: a study of incubation media

1970 ◽  
Vol 48 (4) ◽  
pp. 517-519 ◽  
Author(s):  
I. C. Caldwell ◽  
Marianne F. Chan
Keyword(s):  
Nucleic Acid ◽  
Structural Integrity ◽  
Cell Metabolism ◽  
Ehrlich Ascites Carcinoma ◽  
Leukemic Cells ◽  
Prolonged Incubation ◽  
Ehrlich Ascites ◽  
Eac Cells ◽  
Rna And Dna

A number of incubation media which have been used in studies of the metabolism of Ehrlich ascites carcinoma (EAC) cells in vitro have been examined with respect to their abilities to support the incorporation of radioactive precursors into nucleotides and nucleic acids, and to maintain the structural integrity and tumor-inducing abilities of EAC cells. Cells incubated in the chemically-defined "Fischer's medium for leukemic cells of mice" were able to produce lethal tumors in mice after more than 16 h of incubation, maintained their structural integrity on prolonged incubation, and catalyzed high rates of incorporation of exogenously added substrates into nucleotides, RNA, and DNA. However, cells incubated in balanced salts solutions supplemented with glucose had these characteristics: (a) were unable to produce lethal tumors after 4 h of incubation, (b) released large amounts of nucleotide, nucleic acid, and protein material into the medium after less than 2 h of incubation, and (c) catalyzed the incorporation of radioactive precursors into nucleotides and RNA at much lower rates than did cells incubated in Fischer's medium, and were virtually unable to catalyze the incorporation of adenine-14C into DNA.

scholarly journals Povidone-Iodine Attenuates Viral Replication in Ocular Cells: Implications for Ocular Transmission of RNA Viruses

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 753
Author(s):  
Sneha Singh ◽  
Onkar B. Sawant ◽  
Shahzad I. Mian ◽  
Ashok Kumar
Keyword(s):  
Epithelial Cells ◽  
Viral Replication ◽  
Povidone Iodine ◽  
Rna Viruses ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Host Cells ◽  
Eye Banking ◽  
Antiviral Effects ◽  
Infected Cells

Several RNA viruses, including SARS-CoV-2, can infect or use the eye as an entry portal to cause ocular or systemic diseases. Povidone-Iodine (PVP-I) is routinely used during ocular surgeries and eye banking as a cost-effective disinfectant due to its broad-spectrum antimicrobial activity, including against viruses. However, whether PVP-I can exert antiviral activities in virus-infected cells remains elusive. In this study, using Zika (ZIKV) and Chikungunya (CHIKV) virus infection of human corneal and retinal pigment epithelial cells, we report antiviral mechanisms of PVP-I. Our data showed that PVP-I, even at the lowest concentration (0.01%), drastically reduced viral replication in corneal and retinal cells without causing cellular toxicity. Antiviral effects of PVP-I against ZIKV and CHIKV were mediated by direct viral inactivation, thus attenuating the ability of the virus to infect host cells. Moreover, one-minute PVP-I exposure of infected ocular cells drastically reduced viral replication and the production of infectious progeny virions. Furthermore, viral-induced (CHIKV) expression of inflammatory genes (TNF-α, IL-6, IL-8, and IL1β) were markedly reduced in PVP-I treated corneal epithelial cells. Together, our results demonstrate potent antiviral effects of PVP-I against ZIKV and CHIKV infection of ocular cells. Thus, a low dose of PVP-I can be used during tissue harvesting for corneal transplants to prevent potential transmission of RNA viruses via infected cells.

scholarly journals Nucleic Acid Strand Displacement with Synthetic mRNA Inputs in Living Mammalian Cells

2018 ◽  
Vol 7 (12) ◽  
pp. 2737-2741 ◽  
Author(s):  
Gourab Chatterjee ◽  
Yuan-Jyue Chen ◽  
Georg Seelig
Keyword(s):  
Nucleic Acid ◽  
Mammalian Cells ◽  
Strand Displacement ◽  
Synthetic Mrna

scholarly journals Bat Red Blood Cells express Nucleic Acid Sensing Receptors and bind RNA and DNA

2022 ◽  
Author(s):  
LK Metthew Lam ◽  
Jane Dobkin ◽  
Kaitlyn A. Eckart ◽  
Ian Gereg ◽  
Andrew DiSalvo ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Red Blood Cells ◽  
Immune Function ◽  
Blood Cells ◽  
Toll Like Receptors ◽  
Cpg Dna ◽  
Human Rbcs ◽  
Insight Into ◽  
Rna And Dna

Red blood cells (RBCs) demonstrate immunomodulatory capabilities through the expression of nucleic acid sensors. Little is known about bat RBCs, and no studies have examined the immune function of bat erythrocytes. Here we show that bat RBCs express the nucleic acid-sensing Toll-like receptors TLR7 and TLR9 and bind the nucleic acid ligands, single-stranded RNA, and CpG DNA. Collectively, these data suggest that, like human RBCs, bat erythrocytes possess immune function and may be reservoirs for nucleic acids. These findings provide unique insight into bat immunity and may uncover potential mechanisms by which virulent pathogens in humans are concealed in bats.

scholarly journals Cleavage of DNA and RNA by PLD3 and PLD4 limits autoinflammatory triggering by multiple sensors

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Amanda L. Gavin ◽  
Deli Huang ◽  
Tanya R. Blane ◽  
Therese C. Thinnes ◽  
Yusuke Murakami ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Inflammatory Diseases ◽  
Type I ◽  
Multiple Sensors ◽  
Dna And Rna ◽  
Elevated Type ◽  
Minor Contribution ◽  
Ifn Γ ◽  
A Minor ◽  
Rna And Dna

AbstractPhospholipase D3 (PLD3) and PLD4 polymorphisms have been associated with several important inflammatory diseases. Here, we show that PLD3 and PLD4 digest ssRNA in addition to ssDNA as reported previously. Moreover, Pld3−/−Pld4−/− mice accumulate small ssRNAs and develop spontaneous fatal hemophagocytic lymphohistiocytosis (HLH) characterized by inflammatory liver damage and overproduction of Interferon (IFN)-γ. Pathology is rescued in Unc93b13d/3dPld3−/−Pld4−/− mice, which lack all endosomal TLR signaling; genetic codeficiency or antibody blockade of TLR9 or TLR7 ameliorates disease less effectively, suggesting that both RNA and DNA sensing by TLRs contributes to inflammation. IFN-γ made a minor contribution to pathology. Elevated type I IFN and some other remaining perturbations in Unc93b13d/3dPld3−/−Pld4−/− mice requires STING (Tmem173). Our results show that PLD3 and PLD4 regulate both endosomal TLR and cytoplasmic/STING nucleic acid sensing pathways and have implications for the treatment of nucleic acid-driven inflammatory disease.

scholarly journals Modular barcode beads for microfluidic single cell genomics

2020 ◽  
Author(s):  
Cyrille L. Delley ◽  
Adam R. Abate
Keyword(s):  
Nucleic Acid ◽  
Dna Sequencing ◽  
Single Cell ◽  
Optimized Design ◽  
Single Cell Genomics ◽  
New Targets ◽  
Novel Targets ◽  
Rna And Dna ◽  
Modular Framework

AbstractBarcode beads allow efficient nucleic acid tagging in single cell genomics. Current barcode designs, however, are fabricated with a particular application in mind. Repurposing to novel targets, or altering to add additional targets as information is obtained is possible but the result is suboptimal. Here, we describe a modular framework that simplifies generation of multifunctional beads and allows their easy extension to new targets.One Sentence SummaryWe describe an optimized design for barcoding beads which are useful for single cell RNA and DNA sequencing.

THE EFFECT OF ADRENOCORTICOTROPHIN ON THE NUCLEIC ACID METABOLISM OF THE RAT ADRENAL GLAND

1965 ◽  
Vol 32 (3) ◽  
pp. 303-312 ◽  
Author(s):  
R. C. IMRIE ◽  
T. R. RAMAIAH ◽  
F. ANTONI ◽  
W. C. HUTCHISON
Keyword(s):  
Nucleic Acid ◽  
Adrenal Gland ◽  
Dna Content ◽  
Adrenal Glands ◽  
Acid Metabolism ◽  
Female Rats ◽  
Nucleic Acid Metabolism ◽  
Prolonged Administration ◽  
Total Rna ◽  
Rna And Dna

SUMMARY Treatment of female rats with adrenocorticotrophin (ACTH) increased the RNA content of the adrenal glands progressively during a period of 3 days, the DNA content increased only after prolonged administration. By contrast, ACTH caused a decrease in the uptake of [32P]orthophosphate into the total RNA of the gland and into most of the RNA fractions of the subcellular components. A method of analysis for RNA and DNA based on the Schmidt-Thannhauser procedure has been evolved which eliminates extraction of nucleic acid by lipid solvents.

scholarly journals γ-TRIS: a graph-algorithm for comprehensive identification of vector genomic insertion sites

2019 ◽  
Author(s):  
Andrea Calabria ◽  
Stefano Beretta ◽  
Ivan Merelli ◽  
Giulio Spinozzi ◽  
Stefano Brasca ◽  
...  
Keyword(s):  
Predictive Power ◽  
Graph Algorithm ◽  
Low Complexity ◽  
Host Cells ◽  
Supplementary Information ◽  
Dna Junctions ◽  
Alignment Tool ◽  
Insertion Sites ◽  
Cell Genome

Abstract Summary Retroviruses and their vector derivatives integrate semi-randomly in the genome of host cells and are inherited by their progeny as stable genetic marks. The retrieval and mapping of the sequences flanking the virus-host DNA junctions allows the identification of insertion sites in gene therapy or virally infected patients, essential for monitoring the evolution of genetically modified cells in vivo. However, since ∼30% of insertions land in low complexity or repetitive regions of the host cell genome, they cannot be correctly assigned and are currently discarded, limiting the accuracy and predictive power of clonal tracking studies. Here, we present γ-TRIS, a new graph-based genome-free alignment tool for identifying insertion sites even if embedded in low complexity regions. By using γ-TRIS to reanalyze clinical studies, we observed improvements in clonal quantification and tracking. Availability and implementation Source code at https://bitbucket.org/bereste/g-tris. Contact [email protected] Supplementary information Supplementary data are available at Bioinformatics online.

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