ArticleNature biotechnology2023
An engineered T7 RNA polymerase that produces mRNA free of immunostimulatory byproducts.
Article in Nature biotechnology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
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Who cites it
130 citing papers in PubMed, 206 citations in OpenAlex.
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- Towards mRNA therapeutics 2.0.Nature reviews. Drug discovery · 2026Review
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- Molecular Basis of pH-Dependent Activity in T7 RNA Polymerase Revealed by Constant pH Replica Exchange Molecular Dynamics.ACS physical chemistry Au · 2026Article
- Cold-adapted RNA polymerase fromProceedings of the National Academy of Sciences of the United States of America · 2026Article
- A G-Quadruplex-Activated Near-Infrared Chemiluminescent Probe for In Situ Hepatic Imaging of the Hepatitis C Virus Genome.Angewandte Chemie (International ed. in English) · 2026Article
- Distinguishing self from non-self RNA by editing-specific inosine patterns.Nucleic acids research · 2026Article
- A Luciferase-Based Assay for Assessing Cap-Independent Translation in Wheat Germ Extract.Bio-protocol · 2026Article
- Fluorogenic RNA Aptamer-Based Activity Quantification of T7 RNA Polymerase.Biochemistry · 2026Article
- Fluorescence-Activated Cell Sorting Enables Rapid Screening of RNA Polymerase-Promoter Interaction in E. coli.Biochemistry · 2026Article
- NNature · 2026Article
- Two Classes of Protein Therapeutics: Why Dose-Response Architecture Defines the Boundary of mRNA Medicines.Pharmaceutics · 2026Review
- The current landscape of mRNA therapy and the strategies for mRNA purification and dsRNA removal.Journal of biomedical science · 2026Review
- IVT-free, chemically synthesized protein-encoding RNA oligonucleotides for rapid production of personalized cancer vaccines.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A Modular Mechanistic In Silico Model for In Vitro Transcription Process Yield and Product Quality Prediction.Biotechnology and bioengineering · 2026Article
- Engineered circular RNA compatible with complete nucleoside modification and rolling circle translation through a Cap-independent translation enhancer.Nature biomedical engineering · 2026Article
- Analytical Characterization and Stability Assessment of RNA-Based Vaccines.Pharmaceutics · 2026Review
- Programming the immunological properties of mRNA vaccines for cancer.Nature reviews. Immunology · 2026Review
- Engineered T7 RNA polymerase to improve mRNA capping efficiency and reduce dsRNA generation duringMolecular therapy. Advances · 2026Article
70 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In vitro transcription (IVT) is a DNA-templated process for synthesizing long RNA transcripts, including messenger RNA (mRNA). For many research and commercial applications, IVT of mRNA is typically performed using bacteriophage T7 RNA polymerase (T7 RNAP) owing to its ability to produce full-length RNA transcripts with high fidelity; however, T7 RNAP can also produce immunostimulatory byproducts such as double-stranded RNA that can affect protein expression. Such byproducts require complex purification processes, using methods such as reversed-phase high-performance liquid chromatography, to yield safe and effective mRNA-based medicines. To minimize the need for downstream purification processes, we rationally and computationally engineered a double mutant of T7 RNAP that produces substantially less immunostimulatory RNA during IVT compared with wild-type T7 RNAP. The resulting mutant allows for a simplified production process with similar mRNA potency, lower immunostimulatory content and quicker manufacturing time compared with wild-type T7 RNAP. Herein, we describe the computational design and development of this improved T7 RNAP variant.
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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.