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Self-amplifying mRNA-Based Vaccine Technology and Its Mode of Action

https://doi.org/10.1007/82_2021_233

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Formulation and Delivery Technologies for mRNA Vaccines

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Self-Replicating RNA

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Alphavirus-Based Vaccines

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HPLC Purification of In Vitro Transcribed Long RNA

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mRNA as novel technology for passive immunotherapy

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Self-Amplifying mRNA Vaccines

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Pathogen Recognition and Innate Immunity

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The Many Pathways of RNA Degradation

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Germinal center enhancement by extended antigen availability

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Alphaviruses suppress host immunity by preventing myeloid cell replication and antagonizing innate immune responses

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IFIT1: A dual sensor and effector molecule that detects non-2′-O methylated viral RNA and inhibits its translation

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Complex Modulation of Cell Type-Specific Signaling in Response to Type I Interferons

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Vaccine Adjuvants: Putting Innate Immunity to Work

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Elicitation of Robust Tier 2 Neutralizing Antibody Responses in Nonhuman Primates by HIV Envelope Trimer Immunization Using Optimized Approaches

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Innate immune response and programmed cell death following carrier-mediated delivery of unmodified mRNA to respiratory cells

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Effect of complexing lipids on cellular uptake and expression of messenger RNA in human skin explants

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Type I Interferons Modulate CD8 + T Cell Immunity to mRNA Vaccines

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Polyethylenimine-based polyplex delivery of self-replicating RNA vaccines

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Intramuscular Delivery of Replicon RNA Encoding ZIKV-117 Human Monoclonal Antibody Protects against Zika Virus Infection

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Rapid, Single-Cell Analysis and Discovery of Vectored mRNA Transfection In Vivo with a loxP-Flanked tdTomato Reporter Mouse

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Self-Amplifying Replicon RNA Delivery to Dendritic Cells by Cationic Lipids

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Proximity Ligation Assays for In Situ Detection of Innate Immune Activation: Focus on In Vitro-Transcribed mRNA

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A Facile Method for the Removal of dsRNA Contaminant from In Vitro-Transcribed mRNA

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Neutral Lipopolyplexes for In Vivo Delivery of Conventional and Replicative RNA Vaccine

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Expression Kinetics and Innate Immune Response after Electroporation and LNP-Mediated Delivery of a Self-Amplifying mRNA in the Skin

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RNA: The new revolution in nucleic acid vaccines

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Regulation of stress granules in virus systems

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Randomized, double-blind, Phase 1 trial of an alphavirus replicon vaccine for cytomegalovirus in CMV seronegative adult volunteers

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Infected dendritic cells are sufficient to mediate the adjuvant activity generated by Venezuelan equine encephalitis virus replicon particles

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Prime-boost vaccine strategy against viral infections: Mechanisms and benefits

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Immunogenicity and protective efficacy induced by self-amplifying mRNA vaccines encoding bacterial antigens

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Co-administration of GM-CSF expressing RNA is a powerful tool to enhance potency of SAM-based vaccines

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mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials

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Proof-of-concept of a low-dose unmodified mRNA-based rabies vaccine formulated with lipid nanoparticles in human volunteers: A phase 1 trial

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Characterization of purified Sindbis virus nsP4 RNA-dependent RNA polymerase activity in vitro

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The 5′UTR-specific mutation in VEEV TC-83 genome has a strong effect on RNA replication and subgenomic RNA synthesis, but not on translation of the encoded proteins

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Engineered alphavirus replicon vaccines based on known attenuated viral mutants show limited effects on immunogenicity

inferredcites →https://doi.org/10.1016/j.virol.2015.04.023openalex-snapshot

Control of alphavirus-based gene expression using engineered riboswitches

inferredcites →https://doi.org/10.1016/j.virol.2016.06.005openalex-snapshot

Host translation shutoff mediated by non-structural protein 2 is a critical factor in the antiviral state resistance of Venezuelan equine encephalitis virus

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The 5′ and 3′ ends of alphavirus RNAs – Non-coding is not non-functional

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Alphavirus polymerase and RNA replication

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Addressing the Cold Reality of mRNA Vaccine Stability

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Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses

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Efficient Targeting and Activation of Antigen-Presenting Cells In Vivo after Modified mRNA Vaccine Administration in Rhesus Macaques

inferredcites →https://doi.org/10.1016/j.ymthe.2017.11.017openalex-snapshot

Self-Amplifying RNA Vaccines Give Equivalent Protection against Influenza to mRNA Vaccines but at Much Lower Doses

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A Nanostructured Lipid Carrier for Delivery of a Replicating Viral RNA Provides Single, Low-Dose Protection against Zika

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mRNA-Based Protein Replacement Therapy for the Heart

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mRNA-Based Genetic Reprogramming

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Delivery of mRNA Therapeutics for the Treatment of Hepatic Diseases

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Self-Amplifying RNA Vaccines for Venezuelan Equine Encephalitis Virus Induce Robust Protective Immunogenicity in Mice

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Genome Editing with mRNA Encoding ZFN, TALEN, and Cas9

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mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases

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Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery

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Immunogenicity of RNA Replicons Encoding HIV Env Immunogens Designed for Self-Assembly into Nanoparticles

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A Trans-amplifying RNA Vaccine Strategy for Induction of Potent Protective Immunity

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In Vivo Validation of a Reversible Small Molecule-Based Switch for Synthetic Self-Amplifying mRNA Regulation

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Innate Inhibiting Proteins Enhance Expression and Immunogenicity of Self-Amplifying RNA

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Nonclinical safety assessment of repeated administration and biodistribution of a novel rabies self-amplifying mRNA vaccine in rats

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Semliki Forest virus vectors for rapid and high-level expression of integral membrane proteins

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RNA helicase activity of Semliki Forest virus replicase protein NSP2

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Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial

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Novel semliki forest virus vectors with reduced cytotoxicity and temperature sensitivity for long-term enhancement of transgene expression

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Cis-acting RNA elements at the 5′ end of Sindbis virus genome RNA regulate minus- and plus-strand RNA synthesis

inferredcites →https://doi.org/10.1021/acs.biomac.0c00445openalex-snapshot

Mannosylated Poly(ethylene imine) Copolymers Enhance saRNA Uptake and Expression in Human Skin Explants

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Comparison of the Expression Kinetics and Immunostimulatory Activity of Replicating mRNA, Nonreplicating mRNA, and pDNA after Intradermal Electroporation in Pigs

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Monitoring Translation Activity of mRNA-Loaded Nanoparticles in Mice

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Mannosylation of LNP Results in Improved Potency for Self-Amplifying RNA (SAM) Vaccines

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Big Is Beautiful: Enhanced saRNA Delivery and Immunogenicity by a Higher Molecular Weight, Bioreducible, Cationic Polymer

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Dendritic Cell Targeting mRNA Lipopolyplexes Combine Strong Antitumor T-Cell Immunity with Improved Inflammatory Safety

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The Skin You Are In: Design-of-Experiments Optimization of Lipid Nanoparticle Self-Amplifying RNA Formulations in Human Skin Explants

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RNA Replicon Delivery via Lipid-Complexed PRINT Protein Particles

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TLR signaling in B-cell development and activation

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How COVID unlocked the power of RNA vaccines

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Rapidly produced SAM ® vaccine against H7N9 influenza is immunogenic in mice

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Action and Reaction: The Biological Response to siRNA and Its Delivery Vehicles

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Type I IFN Counteracts the Induction of Antigen-Specific Immune Responses by Lipid-Based Delivery of mRNA Vaccines

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A Cationic Nanoemulsion for the Delivery of Next-generation RNA Vaccines

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Type I Interferons Interfere with the Capacity of mRNA Lipoplex Vaccines to Elicit Cytolytic T Cell Responses

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Self-replicating Replicon-RNA Delivery to Dendritic Cells by Chitosan-nanoparticles for Translation In Vitro and In Vivo

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Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses

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Mammalian synthetic circuits with RNA binding proteins for RNA-only delivery

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Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA

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A New Generation of Animal Cell Expression Vectors Based on the Semliki Forest Virus Replicon

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An RNA toolbox for cancer immunotherapy

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Knocking down barriers: advances in siRNA delivery

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mRNA-based therapeutics — developing a new class of drugs

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The broad-spectrum antiviral functions of IFIT and IFITM proteins

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Inside out: optimization of lipid nanoparticle formulations for exterior complexation and in vivo delivery of saRNA

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Self-amplifying RNA vaccines for infectious diseases

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Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection

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Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice

inferredcites →https://doi.org/10.1038/s41541-017-0032-6openalex-snapshot

Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines

inferredcites →https://doi.org/10.1038/s41551-019-0378-3openalex-snapshot

Visualization of early events in mRNA vaccine delivery in non-human primates via PET–CT and near-infrared imaging

inferredcites →https://doi.org/10.1038/s41564-019-0421-xopenalex-snapshot

Decoding type I and III interferon signalling during viral infection

inferredcites →https://doi.org/10.1038/s41586-020-2639-4openalex-snapshot

Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults

inferredcites →https://doi.org/10.1038/s41586-020-2814-7openalex-snapshot

COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses

inferredcites →https://doi.org/10.1038/s41589-018-0146-9openalex-snapshot

Small-molecule-based regulation of RNA-delivered circuits in mammalian cells

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An RNA nanoparticle vaccine against Zika virus elicits antibody and CD8+ T cell responses in a mouse model

inferredcites →https://doi.org/10.1038/s41598-018-26281-zopenalex-snapshot

Codon optimization and improved delivery/immunization regimen enhance the immune response against wild-type and drug-resistant HIV-1 reverse transcriptase, preserving its Th2-polarity

inferredcites →https://doi.org/10.1038/s41598-018-30784-0openalex-snapshot

Characterization of induced tissue-specific stem cells from pancreas by a synthetic self-replicative RNA

inferredcites →https://doi.org/10.1038/s41598-019-43422-0openalex-snapshot

In vitro evolution of enhanced RNA replicons for immunotherapy

inferredcites →https://doi.org/10.1038/sj.gt.3302620openalex-snapshot

Biology and application of alphaviruses in gene therapy

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Mechanism of activation of the double‐stranded‐RNA‐dependent protein kinase, PKR

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A Cell-Based, High-Throughput Screen for Small Molecule Regulators of Hepatitis C Virus Replication

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Durability of Responses after SARS-CoV-2 mRNA-1273 Vaccination

inferredcites →https://doi.org/10.1056/nejmoa2022483openalex-snapshot

An mRNA Vaccine against SARS-CoV-2 — Preliminary Report

inferredcites →https://doi.org/10.1056/nejmoa2027906openalex-snapshot

Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates

inferredcites →https://doi.org/10.1056/nejmoa2028436openalex-snapshot

Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults

inferredcites →https://doi.org/10.1056/nejmoa2034577openalex-snapshot

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

inferredcites →https://doi.org/10.1073/pnas.111163898openalex-snapshot

Biologic consequences of Stat1-independent IFN signaling

inferredcites →https://doi.org/10.1073/pnas.1209367109openalex-snapshot

Nonviral delivery of self-amplifying RNA vaccines

inferredcites →https://doi.org/10.1073/pnas.1401662111openalex-snapshot

Type I interferon suppresses de novo virus-specific CD4 Th1 immunity during an established persistent viral infection

inferredcites →https://doi.org/10.1073/pnas.1600299113openalex-snapshot

Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose

inferredcites →https://doi.org/10.1073/pnas.1606050113openalex-snapshot

Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination

inferredcites →https://doi.org/10.1073/pnas.1712377114openalex-snapshot

Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains

inferredcites →https://doi.org/10.1073/pnas.1908052116openalex-snapshot

mRNA structure regulates protein expression through changes in functional half-life

inferredcites →https://doi.org/10.1073/pnas.92.2.507openalex-snapshot

Reaction in alphavirus mRNA capping: formation of a covalent complex of nonstructural protein nsP1 with 7-methyl-GMP.

inferredcites →https://doi.org/10.1074/jbc.270.11.6298openalex-snapshot

Self-coded 3′-Extension of Run-off Transcripts Produces Aberrant Products during in Vitro Transcription with T7 RNA Polymerase

inferredcites →https://doi.org/10.1074/jbc.m307481200openalex-snapshot

Regulation of the Sequential Processing of Semliki Forest Virus Replicase Polyprotein

inferredcites →https://doi.org/10.1080/14760584.2019.1640117openalex-snapshot

Novel prime-boost vaccine strategies against HIV-1

inferredcites →https://doi.org/10.1080/21645515.2016.1227900openalex-snapshot

Human transcriptome response to immunization with live-attenuated Venezuelan equine encephalitis virus vaccine (TC-83): Analysis of whole blood

inferredcites →https://doi.org/10.1084/jem.20080091openalex-snapshot

Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid–inducible gene-I and melanoma differentiation–associated gene 5

inferredcites →https://doi.org/10.1084/jem.20090851openalex-snapshot

Type I IFN controls chikungunya virus via its action on nonhematopoietic cells

inferredcites →https://doi.org/10.1086/319857openalex-snapshot

Self‐Replicative RNA Vaccines Elicit Protection against Influenza A Virus, Respiratory Syncytial Virus, and a Tickborne Encephalitis Virus

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Effects of Self-Complementarity, Codon Optimization, Transgene, and Dose on Liver Transduction with AAV8

inferredcites →https://doi.org/10.1089/hum.2017.121openalex-snapshot

Improvement of In Vivo Expression of Genes Delivered by Self-Amplifying RNA Using Vaccinia Virus Immune Evasion Proteins

inferredcites →https://doi.org/10.1089/hum.2018.145openalex-snapshot

Purification of mRNA Encoding Chimeric Antigen Receptor Is Critical for Generation of a Robust T-Cell Response

inferredcites →https://doi.org/10.1089/jir.2010.0120openalex-snapshot

New Insights into the Role of RNase L in Innate Immunity

inferredcites →https://doi.org/10.1089/nat.2017.0697openalex-snapshot

Leveraging Rational Protein Engineering to Improve mRNA Therapeutics

inferredcites →https://doi.org/10.1093/infdis/jiu522openalex-snapshot

Potent Immune Responses in Rhesus Macaques Induced by Nonviral Delivery of a Self-amplifying RNA Vaccine Expressing HIV Type 1 Envelope With a Cationic Nanoemulsion

inferredcites →https://doi.org/10.1093/nar/12.12.5123openalex-snapshot

Production of infectious poliovirus from cloned cDNA is dramatically increased by SV40 transcription and replication signals

inferredcites →https://doi.org/10.1093/nar/15.21.8783openalex-snapshot

Oligoribonucleotide synthesis using T7 RNA polymerase and synthetic DNA templates

inferredcites →https://doi.org/10.1093/nar/23.9.1495openalex-snapshot

A sindbis virus mRNA polynucleotide vector achieves prolonged and high level heterologous gene expressionin vivo

inferredcites →https://doi.org/10.1093/nar/gkp059openalex-snapshot

The regulatory domain of the RIG-I family ATPase LGP2 senses double-stranded RNA

inferredcites →https://doi.org/10.1093/nar/gkr695openalex-snapshot

Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA

inferredcites →https://doi.org/10.1093/nar/gkt1321openalex-snapshot

Inhibition of translation by IFIT family members is determined by their ability to interact selectively with the 5′-terminal regions of cap0-, cap1- and 5′ppp- mRNAs

inferredcites →https://doi.org/10.1093/nar/gkx290openalex-snapshot

Characterizing exogenous mRNA delivery, trafficking, cytoplasmic release and RNA–protein correlations at the level of single cells

inferredcites →https://doi.org/10.1099/jgv.0.000249openalex-snapshot

Alphavirus RNA synthesis and non-structural protein functions

inferredcites →https://doi.org/10.1099/jgv.0.000448openalex-snapshot

Ability of minus strands and modified plus strands to act as templates in Semliki Forest virus RNA replication

inferredcites →https://doi.org/10.1099/vir.0.071845-0openalex-snapshot

Chikungunya virus non-structural protein 2-mediated host shut-off disables the unfolded protein response

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Single-dose replicating RNA vaccine induces neutralizing antibodies against SARS-CoV-2 in nonhuman primates

inferredcites →https://doi.org/10.1111/imm.12505openalex-snapshot

CD 8 T‐cell priming upon mRNA vaccination is restricted to bone‐marrow‐derived antigen‐presenting cells and may involve antigen transfer from myocytes

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Tfh cells and HIV bnAbs, an immunodominance model of the HIV neutralizing antibody generation problem

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Cancer immunotherapy with mRNA‐transfected dendritic cells

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Host responses to alphavirus infection

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Impact of mRNA chemistry and manufacturing process on innate immune activation

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Development of a potent Zika virus vaccine using self-amplifying messenger RNA

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CD8 + T cells mediate protection against Zika virus induced by an NS3-based vaccine

inferredcites →https://doi.org/10.1126/science.1132505openalex-snapshot

5'-Triphosphate RNA Is the Ligand for RIG-I

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Blockade of Chronic Type I Interferon Signaling to Control Persistent LCMV Infection

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A Viral RNA Structural Element Alters Host Recognition of Nonself RNA

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Direct Gene Transfer into Mouse Muscle in Vivo

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Sindbis Virus: An Efficient, Broad Host Range Vector for Gene Expression in Animal Cells

inferredcites →https://doi.org/10.1126/science.6272391openalex-snapshot

Cloned Poliovirus Complementary DNA Is Infectious in Mammalian Cells

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Type I interferon suppresses virus-specific B cell responses by modulating CD8 + T cell differentiation

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Inflammatory monocytes hinder antiviral B cell responses

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Interferon-driven deletion of antiviral B cells at the onset of chronic infection

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Interfer’n with antibody responses

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Cross-Neutralization of 1918 and 2009 Influenza Viruses: Role of Glycans in Viral Evolution and Vaccine Design

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An Alphavirus -derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates

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Lack of Interference with Immunogenicity of a Chimeric Alphavirus Replicon Particle-Based Influenza Vaccine by Preexisting Antivector Immunity

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Phase I Safety and Immunogenicity Evaluations of an Alphavirus Replicon HIV-1 Subtype C gag Vaccine in Healthy HIV-1-Uninfected Adults

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Assembly of Alphavirus Replication Complexes from RNA and Protein Components in a Novel trans -Replication System in Mammalian Cells

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A Chikungunya Virus trans -Replicase System Reveals the Importance of Delayed Nonstructural Polyprotein Processing for Efficient Replication Complex Formation in Mosquito Cells

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Phosphatidylinositol 3-Kinase-, Actin-, and Microtubule-Dependent Transport of Semliki Forest Virus Replication Complexes from the Plasma Membrane to Modified Lysosomes

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Structural and Functional Elements of the Promoter Encoded by the 5′ Untranslated Region of the Venezuelan Equine Encephalitis Virus Genome

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The C-Terminal Domain of Chikungunya Virus nsP2 Independently Governs Viral RNA Replication, Cytopathicity, and Inhibition of Interferon Signaling

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Chikungunya Virus Nonstructural Protein 2 Inhibits Type I/II Interferon-Stimulated JAK-STAT Signaling

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Venezuelan Equine Encephalitis Virus Disrupts STAT1 Signaling by Distinct Mechanisms Independent of Host Shutoff

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Similarities and Differences in Antagonism of Neuron Alpha/Beta Interferon Responses by Venezuelan Equine Encephalitis and Sindbis Alphaviruses

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Identification and Characterization of Interferon-Induced Proteins That Inhibit Alphavirus Replication

inferredcites →https://doi.org/10.1128/jvi.01441-10openalex-snapshot

Functional Sindbis Virus Replicative Complexes Are Formed at the Plasma Membrane

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Novel Functions of the Alphavirus Nonstructural Protein nsP3 C-Terminal Region

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Role of the Amphipathic Peptide of Semliki Forest Virus Replicase Protein nsP1 in Membrane Association and Virus Replication

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Induction of Broad-Based Immunity and Protective Efficacy by Self-amplifying mRNA Vaccines Encoding Influenza Virus Hemagglutinin

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Purification of Highly Active Alphavirus Replication Complexes Demonstrates Altered Fractionation of Multiple Cellular Membranes

inferredcites →https://doi.org/10.1128/jvi.02073-06openalex-snapshot

The Old World and New World Alphaviruses Use Different Virus-Specific Proteins for Induction of Transcriptional Shutoff

inferredcites →https://doi.org/10.1128/jvi.02411-06openalex-snapshot

Semliki Forest Virus Nonstructural Protein 2 Is Involved in Suppression of the Type I Interferon Response

inferredcites →https://doi.org/10.1128/jvi.02564-07openalex-snapshot

Recruitment of Antigen-Presenting Cells to the Site of Inoculation and Augmentation of Human Immunodeficiency Virus Type 1 DNA Vaccine Immunogenicity by In Vivo Electroporation

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Chikungunya Virus Arthritis in Adult Wild-Type Mice

inferredcites →https://doi.org/10.1128/jvi.03443-13openalex-snapshot

Interferon-Stimulated Poly(ADP-Ribose) Polymerases Are Potent Inhibitors of Cellular Translation and Virus Replication

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Additional file 1 of A critical overview of current progress for COVID-19: development of vaccines, antiviral drugs, and therapeutic antibodies

Editorial review for independent work. ICSAC — the Institute for Complexity Science and Advanced Computing — runs a structured editorial panel for researchers publishing outside journals, and publishes on CiteStamp rails. Submission is free and goes through ORCID: icsacinstitute.org/submit.