ArticleNucleic acids research2018
An origin of the immunogenicity of in vitro transcribed RNA.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
131 citing papers in PubMed, 198 citations in OpenAlex.
- Codon Optimality Modulates Cellular Stress and Innate Immune Responses Triggered by Exogenous RNAs.Journal of molecular biology · 2026Article
- mRNA Therapeutics for Skin Rejuvenation: From Aging Atlases to Clinical Translation.Experimental dermatology · 2026Review
- Cold-adapted RNA polymerase fromProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Beyond the genetic code: orchestrating epigenetic and immune landscapes with multivalent mRNA-exosome vaccines.Precision clinical medicine · 2026Review
- Fluorescence-Activated Cell Sorting Enables Rapid Screening of RNA Polymerase-Promoter Interaction in E. coli.Biochemistry · 2026Article
- Supporting molecular detection of A(H5N1) through development and characterization of RNA reference materials.Analytical and bioanalytical chemistry · 2026Article
- Rational dsRNA design, scalable production and nanodelivery to enhance spray-induced gene silencing.Communications biology · 2026Review
- A Modular Mechanistic In Silico Model for In Vitro Transcription Process Yield and Product Quality Prediction.Biotechnology and bioengineering · 2026Article
- Engineered T7 RNA polymerase to improve mRNA capping efficiency and reduce dsRNA generation duringMolecular therapy. Advances · 2026Article
- Uridine analogs prevent stress granule formation, not by blocking PKR recognition, but by inhibiting the synthesis of T7 RNA polymerase byproducts.RNA (New York, N.Y.) · 2026Article
- A comprehensive analysis of the use of nucleoside analogues in RNA therapeutics.Journal of translational medicine · 2026Review
- Protocol to annotate dendritic cell maturation types in vivo making use of lipid nanoparticle-based approaches.STAR protocols · 2026Article
- Identification of Phage RNA Polymerases That Minimize Double-Stranded RNA By-Product Formation and Their Characterization via In Vitro Transcription.Microorganisms · 2026Article
- Review
- Direct Cytoplasmic Transcription and Trimeric RBD Design Synergize to Enhance DNA Vaccine Potency Against SARS-CoV-2.Pharmaceutics · 2026Article
- Process and analytical strategies for the safe production of mRNA vaccines and therapeutics.Molecular biology reports · 2026Review
- Template nicking suppresses promoter-independent antisense transcription in IVT via R-loop-mediated strand displacement.Nucleic acids research · 2026Article
- Engineering of T7 DNA-dependent RNA polymerase with activity at elevated temperature.PloS one · 2026Article
- Article
- Directed Evolution of T7 RNA Polymerase Minimizes dsRNA By-product and Enables High-Fidelity mRNA Synthesis for Demanding Therapeutic Applications.Research (Washington, D.C.) · 2026Article
71 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The emergence of RNA-based therapeutics demands robust and economical methods to produce RNA with few byproducts from aberrant activity. While in vitro transcription using the bacteriophage T7 RNA polymerase is one such popular method, its transcripts are known to display an immune-stimulatory activity that is often undesirable and uncontrollable. We here showed that the immune-stimulatory activity of T7 transcript is contributed by its aberrant activity to initiate transcription from a promoter-less DNA end. This activity results in the production of an antisense RNA that is fully complementary to the intended sense RNA product, and consequently a long double-stranded RNA (dsRNA) that can robustly stimulate a cytosolic pattern recognition receptor, MDA5. This promoter-independent transcriptional activity of the T7 RNA polymerase was observed for a wide range of DNA sequences and lengths, but can be suppressed by altering the transcription reaction with modified nucleotides or by reducing the Mg2+ concentration. The current work thus not only offers a previously unappreciated mechanism by which T7 transcripts stimulate the innate immune system, but also shows that the immune-stimulatory activity can be readily regulated.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.