ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
In Vivo Validation of a Reversible Small Molecule-Based Switch for Synthetic Self-Amplifying mRNA Regulation.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Influence of the administration route and dose on the expression and antibody responses of a reporter and avian influenza self-amplifying mRNA vaccine in poultry.The veterinary quarterly · 2026Article
- ERAD-level gene switches for on-demand protein secretion and rapidly controlled gene therapies.Nature communications · 2026Article
- Engineering drug-responsive replication machinery for precise control of self-amplifying RNA.Nature biomedical engineering · 2026Article
- Insights into Cardiomyocyte Regeneration from Screening and Transcriptomics Approaches.International journal of molecular sciences · 2026Review
- Antisense oligonucleotide-based switches for conditional translation of synthetic mRNA.Molecular therapy. Nucleic acids · 2025Article
- Engineering gene expression dynamics via self-amplifying RNA with drug-responsive non-structural proteins.bioRxiv : the preprint server for biology · 2025Article
- The advent of clinical self-amplifying RNA vaccines.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Alphaviral backbone of self-amplifying RNA enhances protein expression and immunogenicity against SARS-CoV-2 antigen.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Bridging gene therapy and next-generation vaccine technologies.Gene therapy · 2025Review
- Development of hydrophobic tag purifying monophosphorylated RNA for chemical synthesis of capped mRNA and enzymatic synthesis of circular mRNA.Nucleic acids research · 2024Article
- A comprehensive comparison of DNA and RNA vaccines.Advanced drug delivery reviews · 2024Review
- Advancing in vivo reprogramming with synthetic biology.Current opinion in biotechnology · 2024Review
- Engineered poly(A)-surrogates for translational regulation and therapeutic biocomputation in mammalian cells.Cell research · 2024Article
- Making the Next Generation of Therapeutics: mRNA Meets Synthetic Biology.ACS synthetic biology · 2023Review
- A dual-antigen self-amplifying RNA SARS-CoV-2 vaccine induces potent humoral and cellular immune responses and protects against SARS-CoV-2 variants through T cell-mediated immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Multimeric RNAs for efficient RNA-based therapeutics and vaccines.Journal of controlled release : official journal of the Controlled Release Society · 2022Review
- Demystifying mRNA vaccines: an emerging platform at the forefront of cryptic diseases.RNA biology · 2022Review
- Protein-Based Systems for Translational Regulation of Synthetic mRNAs in Mammalian Cells.Life (Basel, Switzerland) · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Synthetic mRNA therapeutics have the potential to revolutionize healthcare, as they enable patients to produce therapeutic proteins inside their own bodies. However, convenient methods that allow external control over the timing and magnitude of protein production after in vivo delivery of synthetic mRNA are lacking. In this study, we validate the in vivo utility of a synthetic self-amplifying mRNA (RNA replicon) whose expression can be turned off using a genetic switch that responds to oral administration of trimethoprim (TMP), a US Food and Drug Administration (FDA)-approved small-molecule drug. After intramuscular electroporation, the engineered RNA replicon exhibited dose-dependent and reversible expression of its encoded protein upon TMP administration. The TMP serum level needed for maximal downregulation of protein translation was approximately 45-fold below that used in humans for therapeutic purposes. To demonstrate the therapeutic potential of the technology, we injected mice with a TMP-responsive RNA replicon encoding erythropoietin (EPO) and successfully controlled the timing and magnitude of EPO production as well as changes in hematocrit. This work demonstrates the feasibility of controlling mRNA kinetics in vivo, thereby broadly expanding the clinical versatility of mRNA therapeutics.
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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.