ArticleNucleic acids research2011
Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA.
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 501 papers.
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Who cites it
501 citing papers in PubMed, 861 citations in OpenAlex.
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- A Luciferase-Based Assay for Assessing Cap-Independent Translation in Wheat Germ Extract.Bio-protocol · 2026Article
- Nucleoside-Modified mRNA Encoding Alpha-Galactosidase A Ameliorates Fabry Disease Phenotypes in Human IPSC-Derived Cardiomyocytes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The current landscape of mRNA therapy and the strategies for mRNA purification and dsRNA removal.Journal of biomedical science · 2026Review
- Supporting molecular detection of A(H5N1) through development and characterization of RNA reference materials.Analytical and bioanalytical chemistry · 2026Article
- 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
- Thio-modification effects on mRNA translation using a PureCap-based capping method.RSC chemical biology · 2026Article
- Enhanced Intracellular Stability and Translation Efficiency of mRNA Drugs by a 2-arm mRNA Platform.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- Engineered T7 RNA polymerase to improve mRNA capping efficiency and reduce dsRNA generation duringMolecular therapy. Advances · 2026Article
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- Rapid evolution of a highly efficient RNA polymerase by homologous recombination.Nature chemical biology · 2026Article
- Review
- Variability in the TLR3 type I interferon pathway is predictive of RNA vaccine responses.Science advances · 2026Article
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441 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 2 countries.
Funding
Abstract
In vitro-transcribed mRNA has great therapeutic potential to transiently express the encoded protein without the adverse effects of viral and DNA-based constructs. Mammalian cells, however, contain RNA sensors of the innate immune system that must be considered in the generation of therapeutic RNA. Incorporation of modified nucleosides both reduces innate immune activation and increases translation of mRNA, but residual induction of type I interferons (IFNs) and proinflammatory cytokines remains. We identify that contaminants, including double-stranded RNA, in nucleoside-modified in vitro-transcribed RNA are responsible for innate immune activation and their removal by high performance liquid chromatography (HPLC) results in mRNA that does not induce IFNs and inflammatory cytokines and is translated at 10- to 1000-fold greater levels in primary cells. Although unmodified mRNAs were translated significantly better following purification, they still induced high levels of cytokine secretion. HPLC purified nucleoside-modified mRNA is a powerful vector for applications ranging from ex vivo stem cell generation to in vivo gene therapy.
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Registered trials
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