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https://www.readbyqxmd.com/read/29236688/evolution-of-a-designed-protein-assembly-encapsulating-its-own-rna-genome
#1
Gabriel L Butterfield, Marc J Lajoie, Heather H Gustafson, Drew L Sellers, Una Nattermann, Daniel Ellis, Jacob B Bale, Sharon Ke, Garreck H Lenz, Angelica Yehdego, Rashmi Ravichandran, Suzie H Pun, Neil P King, David Baker
The challenges of evolution in a complex biochemical environment, coupling genotype to phenotype and protecting the genetic material, are solved elegantly in biological systems by the encapsulation of nucleic acids. In the simplest examples, viruses use capsids to surround their genomes. Although these naturally occurring systems have been modified to change their tropism and to display proteins or peptides, billions of years of evolution have favoured efficiency at the expense of modularity, making viral capsids difficult to engineer...
December 13, 2017: Nature
https://www.readbyqxmd.com/read/29234790/first-phase-1-trial-of-a-prophylactic-mrna-vaccine-reported
#2
Jennifer Abbasi
No abstract text is available yet for this article.
December 12, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/29232690/rna-interference-in-fasciola-gigantica-establishing-and-optimization-of-experimental-rnai-in-the-newly-excysted-juveniles-of-the-fluke
#3
Arun Anandanarayanan, Opinder Krishen Raina, Hniang Lalrinkima, Ajayta Rialch, Muthu Sankar, Anju Varghese
Fasciolosis caused by Fasciola gigantica is a neglected tropical disease but a constraint on the growth and productivity of cattle, buffaloes and sheep in the tropical countries of Asia and Africa. Resistance to commonly used anthelmintics in Fasciola has increased the need to search for alternative therapeutic targets. RNA interference is the current tool of choice in the search for such targets in Fasciola. The susceptibility of juvenile Fasciola hepatica to double stranded (ds) RNA induced RNAi has been established but in F...
December 12, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29216187/a-thermostable-messenger-rna-based-vaccine-against-rabies
#4
Lothar Stitz, Annette Vogel, Margit Schnee, Daniel Voss, Susanne Rauch, Thorsten Mutzke, Thomas Ketterer, Thomas Kramps, Benjamin Petsch
Although effective rabies virus vaccines have been existing for decades, each year, rabies virus infections still cause around 50.000 fatalities worldwide. Most of these cases occur in developing countries, where these vaccines are not available. The reasons for this are the prohibitive high costs of cell culture or egg grown rabies virus vaccines and the lack of a functional cold chain in many regions in which rabies virus is endemic. Here, we describe the excellent temperature resistance of a non-replicating mRNA based rabies virus vaccine encoding the rabies virus glycoprotein (RABV-G)...
December 7, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29198150/the-effect-of-tumor-derived-exosomes-on-immune-regulation-and-cancer-immunotherapy
#5
Theresa L Whiteside
Tumor-derived exosomes (TEX) carry both immunosuppressive and immunostimulatory receptor/ligands that in part mimic the profiles of the parent tumor cells. Operating as an intercellular communication system, TEX deliver protumor or antitumor signals to immune and nonimmune cells reprogramming their functions. Mechanisms responsible for cellular reprogramming include cell surface signaling and/or uptake of TEX by recipient cells. Once internalized, TEX transfer mRNA, miRNA and proteins that promote transcriptional/translational activities...
December 2017: Future Oncology
https://www.readbyqxmd.com/read/29188369/immune-modulation-of-th1-th2-and-t-reg-transcriptional-factors-differing-from-cytokine-levels-in-schistosoma-japonicum-infection
#6
Amel Farwa, Chao He, Longfei Xia, Hong Zhou
In spite of long-term integrated control programs for Schistosoma japonicum infection in China, the infection is still persistent due to its zoonotic transmission and disease severity which further complicate its control. Th1, Th2, and T-reg cells are involved in S. japonicum immunity; however, their exact roles in immunopathology of this infection are still questionable. Therefore, the monitoring of these T cell subsets' immune responses during a primary infection of S. japonicum at both transcriptional (mRNA) and protein (cytokines) levels would be essential to point out...
November 29, 2017: Parasitology Research
https://www.readbyqxmd.com/read/29181006/protective-effect-of-panax-notoginseng-root-water-extract-against-influenza-a-virus-infection-by-enhancing-antiviral-interferon-mediated-immune-responses-and-natural-killer-cell-activity
#7
Jang-Gi Choi, Young-Hee Jin, Heeeun Lee, Tae Woo Oh, Nam-Hui Yim, Won-Kyung Cho, Jin Yeul Ma
Influenza is an acute respiratory illness caused by the influenza A virus, which causes economic losses and social disruption mainly by increasing hospitalization and mortality rates among the elderly and people with chronic diseases. Influenza vaccines are the most effective means of preventing seasonal influenza, but can be completely ineffective if there is an antigenic mismatch between the seasonal vaccine virus and the virus circulating in the community. In addition, influenza viruses resistant to antiviral drugs are emerging worldwide...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29181005/induction-of-robust-b-cell-responses-after-influenza-mrna-vaccination-is-accompanied-by-circulating-hemagglutinin-specific-icos-pd-1-cxcr3-t-follicular-helper-cells
#8
Gustaf Lindgren, Sebastian Ols, Frank Liang, Elizabeth A Thompson, Ang Lin, Fredrika Hellgren, Kapil Bahl, Shinu John, Olga Yuzhakov, Kimberly J Hassett, Luis A Brito, Hugh Salter, Giuseppe Ciaramella, Karin Loré
Modified mRNA vaccines have developed into an effective and well-tolerated vaccine platform that offers scalable and precise antigen production. Nevertheless, the immunological events leading to strong antibody responses elicited by mRNA vaccines are largely unknown. In this study, we demonstrate that protective levels of antibodies to hemagglutinin were induced after two immunizations of modified non-replicating mRNA encoding influenza H10 encapsulated in lipid nanoparticles (LNP) in non-human primates. While both intradermal (ID) and intramuscular (IM) administration induced protective titers, ID delivery generated this response more rapidly...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29168083/analysis-of-the-cancer-genome-atlas-tcga-database-identifies-an-inverse-relationship-between-interleukin-13-receptor-%C3%AE-1-and-%C3%AE-2-gene-expression-and-poor-prognosis-and-drug-resistance-in-subjects-with-glioblastoma-multiforme
#9
Jing Han, Raj K Puri
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. A variety of targeted agents are being tested in the clinic including cancer vaccines, immunotoxins, antibodies and T cell immunotherapy for GBM. We have previously reported that IL-13 receptor subunits α1 and α2 of IL-13R complex are overexpressed in GBM. We are investigating the significance of IL-13Rα1 and α2 expression in GBM tumors. In order to elucidate a possible relationship between IL-13Rα1 and α2 expression with severity and prognoses of subjects with GBM, we analyzed gene expression (by microarray) and clinical data available at the public The Cancer Genome Atlas (TCGA) database (Currently known as Global Data Commons)...
November 22, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29157813/anti-inflammatory-and-antiviral-activities-of-cynanversicoside-a-and-cynanversicoside-c-isolated-from-cynanchun-paniculatum-in-influenza-a-virus-infected-mice-pulmonary-microvascular-endothelial-cells
#10
Panying Wei, Tao Zhang, Hong Dong, Qiaohong Chen, Xiang Mu, Ge Hu
BACKGROUND: Outbreaks of the influenza A virus (IAV) often occur in various avian and mammalian species, including humans, causing serious respiratory injury worldwide. Therapeutic actions are limited to vaccines and a few antiviral drugs. Combination antiviral compounds and anti-inflammatory modulators to control the propagation of viruses would be more efficient therapeutic strategies for infectious diseases. PURPOSE: This study was designed to isolate anti-inflammatory and antiviral compounds from Cynanchun paniculatum and elucidate their potential molecular mechanisms...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29141136/systemic-mrna-delivery-to-the-lungs-by-functional-polyester-based-carriers
#11
Yunfeng Yan, Hu Xiong, Xinyi Zhang, Qiang Cheng, Daniel John Siegwart
Messenger RNA (mRNA) has recently come into focus as an emerging therapeutic class with great potential for protein replacement therapy, cancer immunotherapy, regenerative medicine, vaccines, and gene editing. However, the lack of effective and safe delivery methods impedes the broad application of mRNA-based therapeutics. Here, we report a robust approach to develop efficient polymeric delivery carriers for mRNA. Lead polyesters were identified by in vitro screening of a 480-member combinatorially modified poly(trimethylolpropane allyl ether-co-suberoyl chloride) library for the delivery of luciferase encoding mRNA (Luc mRNA) to IGROV1 cells...
November 15, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29139478/trigger-happy-resident-memory-cd4-t-cells-inhabit-the-human-lungs
#12
A E Oja, B Piet, C Helbig, R Stark, D van der Zwan, H Blaauwgeers, E B M Remmerswaal, D Amsen, R E Jonkers, P D Moerland, M A Nolte, R A W van Lier, P Hombrink
Resident memory T cells (TRM) reside in the lung epithelium and mediate protective immunity against respiratory pathogens. Although lung CD8(+) TRM have been extensively characterized, the properties of CD4(+) TRM remain unclear. Here we determined the transcriptional signature of CD4(+) TRM, identified by the expression of CD103, retrieved from human lung resection material. Various tissue homing molecules were specifically upregulated on CD4(+) TRM, whereas expression of tissue egress and lymph node homing molecules were low...
November 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29137642/effects-of-mrna-secondary-structure-on-the-expression-of-hev-orf2-proteins-in-escherichia-coli
#13
Nouredine Behloul, Wenjuan Wei, Sarra Baha, Zhenzhen Liu, Jiyue Wen, Jihong Meng
BACKGROUND: Viral protein expression in Escherichia coli (E. coli) is a powerful tool for structural/functional studies as well as for vaccine and diagnostics development. However, numerous factors such as codon bias, mRNA secondary structure and nucleotides distribution, have been indentified to hamper this heterologous expression. RESULTS: In this study, we combined computational and biochemical methods to analyze the influence of these factors on the expression of different segments of hepatitis E virus (HEV) ORF 2 protein and hepatitis B virus surface antigen (HBsAg)...
November 14, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/29132989/differential-gene-expression-elicited-by-children-in-response-to-the-2015-16-live-attenuated-versus-inactivated-influenza-vaccine
#14
Kelly Stefano Cole, Judith M Martin, William T Horne, Chyongchiou J Lin, Mary Patricia Nowalk, John F Alcorn, Richard K Zimmerman
BACKGROUND: In recent influenza seasons, the live attenuated influenza vaccine (LAIV) has not demonstrated the same level of vaccine effectiveness as that observed among children who received the inactivated influenza vaccine (IIV). To better understand this difference, this study compared the mRNA sequencing transcription profile (RNA seq) in children who received either IIV or LAIV. METHODS: Children 3-17years of age receiving quadrivalent influenza vaccine were enrolled...
November 10, 2017: Vaccine
https://www.readbyqxmd.com/read/29121987/sequence-analysis-and-characterization-of-pyruvate-kinase-from-clonorchis-sinensis-a-53-1-kda-homopentamer-implicated-immune-protective-efficacy-against-clonorchiasis
#15
Tingjin Chen, Hongye Jiang, Hengchang Sun, Zhizhi Xie, Pengli Ren, Lu Zhao, Huimin Dong, Mengchen Shi, Zhiyue Lv, Zhongdao Wu, Xuerong Li, Xinbing Yu, Yan Huang, Jin Xu
BACKGROUND: Clonorchis sinensis, the causative agent of clonorchiasis, is classified as one of the most neglected tropical diseases and affects more than 15 million people globally. This hepatobiliary disease is highly associated with cholangiocarcinoma. As key molecules in the infectivity and subsistence of trematodes, glycolytic enzymes have been targets for drug and vaccine development. Clonorchis sinensis pyruvate kinase (CsPK), a crucial glycolytic enzyme, was characterized in this research...
November 9, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29107690/effects-of-oral-and-subcutaneous-administration-of-hsp60-on-myeloid-derived-suppressor-cells-and-atherosclerosis-in-apoe-mice
#16
Yingying Hu, Zhuyue Chen, Lili Jiang, Feng Chen, Runming Jin, Longxian Cheng
HSP60 has been proved to be closely related to atherosclerosis due to its antigenicity. To determine this antigenicity effect, the ApoE-/- mice were fed with western-type diet and HSP60 was administrated orally or subcutaneously (SC) for potential vaccine against atherosclerosis. Here, we observed the ApoE-/- mice with oral HSP60 administration group showed a significant reduction in plaque size at the aortic root; accompanied by increased MSDCs (CD11b(+)Gr1(+)) in peripheral blood and spleen which was mostly composed of M-MDSCs (CD11b(+)LY6G(-)LY6C(high)), and increased plasma IL-10 and splenic Foxp3, Arg1, iNOS mRNA as well as decreased plasma IFN-γ and splenic T-bet mRNA compared to control group...
October 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29100036/nafamostat-mesilate-a-serine-protease-inhibitor-suppresses-interferon-gamma-induced-up-regulation-of-programmed-cell-death-ligand-1-in-human-cancer-cells
#17
Sadamu Homma, Kazumi Hayashi, Kosaku Yoshida, Yukiko Sagawa, Yuko Kamata, Masaki Ito
Programmed cell death ligand-1 (PD-L1) plays a pivotal role in the suppression of antitumour immunity by binding to programmed cell death-1 (PD-1) on tumouricidal cytotoxic T lymphocytes (CTLs), rendering them inactive. As blockade of PD-1/PD-L1 interaction by the monoclonal antibodies induced effective T cell-mediated antitumour response, suppression of PD-L1 expression in tumour cells by the chemical agent might contribute to treatment against malignant tumours. Nafamostat mesilate (NM), a serine protease inhibitor that is frequently used in the clinic, potently suppressed interferon-gamma (IFN-gamma)-induced up-regulation of PD-L1 in cultured human lung cancer cells (HLC-1) at both the messenger RNA (mRNA) and protein levels...
October 28, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29093096/microrna-based-attenuation-of-influenza-virus-across-susceptible-hosts
#18
Barbara M Waring, Louisa E Sjaastad, Jessica K Fiege, Elizabeth J Fay, Ismarc Reyes, Branden Moriarity, Ryan A Langlois
Influenza A virus drives significant morbidity and mortality in humans and livestock. Annual circulation of the virus in livestock and waterfowl contributes to severe economic disruption and increases the risk of zoonotic transmission of novel strains into the human population where there is no preexisting immunity. Seasonal vaccinations in humans help prevent infection and can reduce symptoms when infection does occur. However, current vaccination regimens available for livestock are limited in part due to safety concerns regarding reassortment/recombination with circulating strains...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29071184/nanoliposomes-for-safe-and-efficient-therapeutic-mrna-delivery-a-step-toward-nanotheranostics-in-inflammatory-and-cardiovascular-diseases-as-well-as-cancer
#19
Meike-Kristin Abraham, Karlheinz Peter, Tatjana Michel, Hans Peter Wendel, Stefanie Krajewski, Xiaowei Wang
Rationale: Genetic therapy using modified mRNA for specific therapeutic protein expression for disease treatment and vaccination represents a new field of therapeutic and diagnostic medicine. Non-viral vectors transfection using biocompatible nanoliposomes enables safe and efficient delivery of therapeutic mRNA. Objective: Generation of non-toxic, cell-compatible cationic nanoliposomes as nanotheranostic agents to successfully deliver therapeutic mRNA. Methods and results: Cationic nanoliposomes (DC-Cholesterol/DOPE) were generated as transfection vehicles for either eGFP mRNA or the therapeutic anti-inflammatory, CD39 mRNA...
2017: Nanotheranostics
https://www.readbyqxmd.com/read/29056908/upregulation-of-hla-class-i-expression-on-tumor-cells-by-the-anti-egfr-antibody-nimotuzumab
#20
Greta Garrido, Ailem Rabasa, Cristina Garrido, Lisset Chao, Federico Garrido, Ángel M García-Lora, Belinda Sánchez-Ramírez
Defining how epidermal growth factor receptor (EGFR)-targeting therapies influence the immune response is essential to increase their clinical efficacy. A growing emphasis is being placed on immune regulator genes that govern tumor - T cell interactions. Previous studies showed an increase in HLA class I cell surface expression in tumor cell lines treated with anti-EGFR agents. In particular, earlier studies of the anti-EGFR blocking antibody cetuximab, have suggested that increased tumor expression of HLA class I is associated with positive clinical response...
2017: Frontiers in Pharmacology
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