ArticleNucleic acids research2021
Theoretical basis for stabilizing messenger RNA through secondary structure design.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 114 papers.
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Who cites it
114 citing papers in PubMed, 177 citations in OpenAlex.
- From RNA design to delivery: Computational strategies for functional RNA therapeutics.Bioactive materials · 2027Review
- Domain compositions of Arabidopsis Toll/Interleukin-1 Receptor/Resistance domain-containing TX14 proteins affect localization and induction of the hypersensitive response.Journal of experimental botany · 2026Article
- Towards mRNA therapeutics 2.0.Nature reviews. Drug discovery · 2026Review
- Sindbis virus self-amplifying replicon is compatible with modified nucleotides mediating expression and vaccine responsesMolecular therapy. Advances · 2026Article
- Storage Buffer Composition Impacts Internal Structure, Freeze-Thaw Stability, and Transfection Efficiency of mRNA-Lipid Nanoparticles.ACS nano · 2026Article
- pVACtools v6: A comprehensive suite for neoantigen prediction, visualization, and therapy design.ArXiv · 2026Article
- Fine-scale structural information substantially improves mRNA therapeutic stability prediction.Molecular therapy. Nucleic acids · 2026Article
- Benchmarking reveals the superiority of nucleic acid foundation models in predicting lncRNA coding potential.Genome biology · 2026Article
- Social Justice, Science Agency, and Collaborations: Using Participatory Science to Enhance Learning Outcomes in Postsecondary STEM Courses.CBE life sciences education · 2026Article
- RNA design: update on computational frameworks and programs for inverse RNA folding.Briefings in bioinformatics · 2026Review
- Delivery of mRNA Therapeutics Beyond Infectious Diseases: Design Innovations and Applications in Oncology, Cardiovascular, and Rare Genetic Diseases.Pharmaceuticals (Basel, Switzerland) · 2026Review
- RNA Folding Nearest Neighbor Parameters Including the Modification 1-Methyl-Pseudouridine.bioRxiv : the preprint server for biology · 2026Article
- VaxLab: integrated platform for rapid multistrategy mRNA vaccine design.Experimental & molecular medicine · 2026Article
- Deep learning for RNA secondary structure determination: gauging generalizability and broadening the scope of traditional methods.RNA (New York, N.Y.) · 2026Review
- Article
- SamplingDesign: RNA design via continuous optimization with coupled variables and Monte-Carlo sampling.Nature communications · 2026Article
- Lipid-free, thermostable mRNA vaccines prepared using atomic layer deposition.Journal of pharmaceutical sciences · 2026Article
- Accelerate the Highly Efficient Development of mRNA Vaccines Through Advanced Computational Methods.MedComm · 2026Review
- Article
- Struct2SeQ: RNA inverse folding with Deep Q-Learning.bioRxiv : the preprint server for biology · 2026Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
- Update of
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
RNA hydrolysis presents problems in manufacturing, long-term storage, world-wide delivery and in vivo stability of messenger RNA (mRNA)-based vaccines and therapeutics. A largely unexplored strategy to reduce mRNA hydrolysis is to redesign RNAs to form double-stranded regions, which are protected from in-line cleavage and enzymatic degradation, while coding for the same proteins. The amount of stabilization that this strategy can deliver and the most effective algorithmic approach to achieve stabilization remain poorly understood. Here, we present simple calculations for estimating RNA stability against hydrolysis, and a model that links the average unpaired probability of an mRNA, or AUP, to its overall hydrolysis rate. To characterize the stabilization achievable through structure design, we compare AUP optimization by conventional mRNA design methods to results from more computationally sophisticated algorithms and crowdsourcing through the OpenVaccine challenge on the Eterna platform. We find that rational design on Eterna and the more sophisticated algorithms lead to constructs with low AUP, which we term 'superfolder' mRNAs. These designs exhibit a wide diversity of sequence and structure features that may be desirable for translation, biophysical size, and immunogenicity. Furthermore, their folding is robust to temperature, computer modeling method, choice of flanking untranslated regions, and changes in target protein sequence, as illustrated by rapid redesign of superfolder mRNAs for B.1.351, P.1 and B.1.1.7 variants of the prefusion-stabilized SARS-CoV-2 spike protein. Increases in in vitro mRNA half-life by at least two-fold appear immediately achievable.
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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.