ArticleNature biotechnology2025
Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency.
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Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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59citing papers in PubMed
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Who cites it
59 citing papers in PubMed.
- Bioengineering strategies for improving the immunogenicity of mRNA vaccines.Signal transduction and targeted therapy · 2026Review
- Tuning intracellular immunity by Nodamura virus B2 protein enhances self-amplifying RNA activity.Nature communications · 2026Article
- Sindbis virus self-amplifying replicon is compatible with modified nucleotides mediating expression and vaccine responsesMolecular therapy. Advances · 2026Article
- Engineering mRNA-LNP Medicines for the Ageing Brain: Opportunities and Challenges for Neurodegenerative Diseases.Exploration (Beijing, China) · 2026Review
- Sub-stoichiometric 5-methoxyuridine modification enables tunable immune evasion and protein expression from synthetic mRNAs.Molecular therapy. Nucleic acids · 2026Article
- Cold-adapted RNA polymerase fromProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Transgene sequence codon optimization and composition determines replication competence of self-amplifying RNA.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- From nucleotides to intact transcripts through oligonucleotides: Integrated chromatographic strategies for therapeutic mRNA characterization.Analytical and bioanalytical chemistry · 2026Review
- Pulmonary Delivery of Self-Amplifying RNA: Balancing Inflammation and Durable Transgene Expression.ACS nano · 2026Article
- Genetic Medicine Approaches for Tumor Suppressor Loss: Therapeutic Replacement with Self-Amplifying RNA.Pharmaceutical research · 2026Review
- Alphavirus replicase and regulatory RNA elements in host interactions and viral vector engineering.Journal of virology · 2026Review
- Enhanced Intracellular Stability and Translation Efficiency of mRNA Drugs by a 2-arm mRNA Platform.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Platelet-Targeted Self-Amplifying mRNA for Safe, Long-Acting Thromboprophylaxis.Circulation research · 2026Article
- A self-amplifying RNA vector based on rubella virus for mRNA therapeutics and vaccine applications.Molecular therapy. Nucleic acids · 2026Article
- Single injection of modified self-amplifying RNA encoding a CD19 bispecific T cell engager mediates long-term malignant B cell clearance.bioRxiv : the preprint server for biology · 2026Article
- A comprehensive analysis of the use of nucleoside analogues in RNA therapeutics.Journal of translational medicine · 2026Review
- "More" Artificial mRNAs: Beyond the Art of Nature.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Self-amplifying RNA-based CAR T cell therapy with enhanced duration and multi-genic logic functions.bioRxiv : the preprint server for biology · 2026Article
- Deep learning-guided dual-fitness evolution of T7 RNA polymerase for enhanced stability and activity.Nucleic acids research · 2026Article
- Single intramuscular injection of self-amplifying RNA ofScience (New York, N.Y.) · 2026Article
Corrections and comments
- Update of
Authors and funding
9 authors.
Joshua E McGee *Department of Biomedical Engineering, Boston University, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3327-6209
Jack R Kirsch *Department of Biomedical Engineering, Boston University, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6808-7056
Devin KenneyDepartment of Virology, Immunology and Microbiology, Boston University School of Medicine, Boston, MA, USA.
Faith CerboDepartment of Virology, Immunology and Microbiology, Boston University School of Medicine, Boston, MA, USA.ORCID http://orcid.org/0009-0005-3931-5303
Elizabeth C ChavezDepartment of Virology, Immunology and Microbiology, Boston University School of Medicine, Boston, MA, USA.ORCID http://orcid.org/0000-0003-0252-7140
Ting-Yu ShihDepartment of Chemistry, Boston University, Boston, MA, USA.
Florian DouamDepartment of Virology, Immunology and Microbiology, Boston University School of Medicine, Boston, MA, USA. fdouam@bu.edu.
Wilson W WongDepartment of Biomedical Engineering, Boston University, Boston, MA, USA. wilwong@bu.edu.ORCID http://orcid.org/0000-0001-8394-889X
Mark W GrinstaffDepartment of Biomedical Engineering, Boston University, Boston, MA, USA. mgrin@bu.edu.ORCID http://orcid.org/0000-0002-5453-3668
Funding
RESEARCH TRAINING IN IMMUNOLOGYT32AI007309 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI GUMMULURU, SURYARAM · 1988 to 2024
$7.4MSynthetic toolkit for precision gene expression control and signal processing in mammalian cellsR01EB029483 · NIBIB · HARVARD UNIVERSITY · PI Ahmad Samir Khalil · 2020 to 2026
$5.0MTranslational Research in BiomaterialsT32EB006359 · NIBIB · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI MARK W. GRINSTAFF, Michelle H Teplensky · 2009 to 2026
$4.2MPrecise targeting of T1D specific T cells using CAR and peptide-MHC chimeric antigen ligandsR01DK132576 · NIDDK · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI BIRNBAUM, MICHAEL, CETRULO, CURTIS LISANTE · 2022 to 2025
$2.9MPrecise tumor targeting with logic CAR circuitsU01CA265713 · NCI · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI COLSON, YOLONDA L, GRINSTAFF, MARK W. · 2021 to 2025
$2.5MMultiplexed and Logical Control of the Mammalian Transcriptome Using Cas13R01EB031904 · NIBIB · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI WONG, WILSON · 2021 to 2024
$1.6MHigh Sensitivity In Vivo Imaging System with Integrated Micro-Computed Tomography for Animal Phenotyping CoreS10OD030501 · OD · BOSTON UNIVERSITY MEDICAL CAMPUS · PI SETA, FRANCESCA · 2022 to 2022
$600kEffects of PARP-1 gene deletion in a mouse model of Alzheimer's diseaseR21AG029483 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI SWANSON, RAYMOND A · 2007 to 2008
$411kIn Vivo Imaging Analysis System - Xenogen IVIS SpectrumS10RR024523 · NCRR · BOSTON UNIVERSITY MEDICAL CAMPUS · PI GERSTENFELD, LOUIS CHARLES · 2008 to 2008
$350kCharacterization of a human-specific positive regulator of flavivirus infectionK22AI144050 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI DOUAM, FLORIAN · 2021 to 2023
$344kNCI NIH HHS U01 CA265713NCRR NIH HHS S10 RR024523NIAID NIH HHS K22 AI144050NIAID NIH HHS T32 AI007309NIBIB NIH HHS R01 EB029483NIBIB NIH HHS R01 EB031904NIBIB NIH HHS T32 EB006359NIDDK NIH HHS R01 DK132576NIH HHS S10 OD030501NSF | BIO | Division of Molecular and Cellular Biosciences (MCB) 2234657U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U01CA265713U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) K22AI144050U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) T32AI007309U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB) R01EB029483U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB) R01EB031904U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB) T32EB006359U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) R01DK132576
Abstract
The use of modified nucleotides to suppress the interferon response and maintain translation of self-amplifying RNA (saRNA), which has been achieved for mRNA, has not yet succeeded. We identify modified nucleotides that, when substituted at 100% in saRNA, confer innate immune evasion and robust long-term protein expression, and when formulated as a vaccine, protect against lethal SARS-CoV-2 challenge in mice. This discovery advances saRNA therapeutics by enabling prolonged protein expression at low doses.
Indexed as
COVID-19COVID-19 VaccinesInterferonsNucleotidesRNA, ViralSARS-CoV-2AnimalsHumansImmunity, InnateMiceRNA, MessengerCOVID-19 VaccinesInterferonsNucleotidesRNA, MessengerRNA, Viral
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