ArticleNature communications2022
Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 229 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
229 citing papers in PubMed.
- From RNA design to delivery: Computational strategies for functional RNA therapeutics.Bioactive materials · 2027Review
- Self-amplifying RNA (saRNA) and circular RNA (circRNA) vaccines: Progress, evidence gaps, and translational pathways for durable and scalable immunization.Human vaccines & immunotherapeutics · 2026Review
- Structure-driven function of plant lncRNAs: conserved RNA architectures in transcriptional and post-transcriptional regulation.RNA biology · 2026Review
- Bioengineering strategies for improving the immunogenicity of mRNA vaccines.Signal transduction and targeted therapy · 2026Review
- Towards mRNA therapeutics 2.0.Nature reviews. Drug discovery · 2026Review
- mRNA lipid nanoparticle vaccines: current status, challenges and future prospects.Molecular biomedicine · 2026Review
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- Microfluidics-mediated spatial control of mRNA lipid nanoparticles primes translation and enhances vaccine potency.Nature biomedical engineering · 2026Article
- Circular Photocaged mRNA for Light-induced Late-stage Activation of Translation.Angewandte Chemie (International ed. in English) · 2026Article
- Streamlined synthetic regulatory cassette for efficient and photoreceptor-enriched retinal gene expression.Molecular therapy. Nucleic acids · 2026Article
- Improving recombinant protein productivity in CHO cells via multi-omics data integration.Bioresources and bioprocessing · 2026Review
- Deciphering the comprehensive relationship between 5' UTR and 3' UTR sequences with deep learning.Bioinformatics (Oxford, England) · 2026Article
- Spatial mapping of RNA turnover kinetics in the mouse brain.Nature neuroscience · 2026Article
- Enhanced antitumor immunity of mRNA vaccines by bioorthogonal-like delayed activation of exogeneous STING.Nature biotechnology · 2026Article
- Bacterial mRNA Vaccines: Programming Immunity Against Antimicrobial Resistance.Drug development research · 2026Review
- Two Classes of Protein Therapeutics: Why Dose-Response Architecture Defines the Boundary of mRNA Medicines.Pharmaceutics · 2026Review
- Messenger RNA and guide RNA distributions in lipid nanoparticles impact gene-editing efficiency in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- seq2ribo: structure-aware integration of machine learning and simulation to predict ribosome location profiles from RNA sequences.Bioinformatics (Oxford, England) · 2026Article
- Tunable Lipid Coatings Enable Cytoplasmic siRNA Delivery by DNA Origami.ACS applied materials & interfaces · 2026Article
- A bivalent mRNA-LNP vaccine confers broad-spectrum protection against both homologous and heterologous H5/H7 highly pathogenic avian influenza viruses in SPF chickens.Veterinary research · 2026Article
169 more citing papers are in PubMed but not listed here.
Corrections and comments
- Update of
Authors and funding
29 authors.
Funding
Abstract
Therapeutic mRNAs and vaccines are being developed for a broad range of human diseases, including COVID-19. However, their optimization is hindered by mRNA instability and inefficient protein expression. Here, we describe design principles that overcome these barriers. We develop an RNA sequencing-based platform called PERSIST-seq to systematically delineate in-cell mRNA stability, ribosome load, as well as in-solution stability of a library of diverse mRNAs. We find that, surprisingly, in-cell stability is a greater driver of protein output than high ribosome load. We further introduce a method called In-line-seq, applied to thousands of diverse RNAs, that reveals sequence and structure-based rules for mitigating hydrolytic degradation. Our findings show that highly structured "superfolder" mRNAs can be designed to improve both stability and expression with further enhancement through pseudouridine nucleoside modification. Together, our study demonstrates simultaneous improvement of mRNA stability and protein expression and provides a computational-experimental platform for the enhancement of mRNA medicines.
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What Socratic 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 Socratic graph.