ArticleNature communications2021
High-throughput 5' UTR engineering for enhanced protein production in non-viral gene therapies.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
What it found
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Who cites it
88 citing papers in PubMed, 151 citations in OpenAlex.
- From RNA design to delivery: Computational strategies for functional RNA therapeutics.Bioactive materials · 2027Review
- Large serine recombinase-mediated gene insertion for high-throughput screens: advantages, design principles, and applications.Nucleic acids research · 2026Review
- Site-specific gene integration by recombinase-mediated cassette exchange in anhydrobiotic Pv11 cells.In vitro cellular & developmental biology. Animal · 2026Article
- Deciphering the comprehensive relationship between 5' UTR and 3' UTR sequences with deep learning.Bioinformatics (Oxford, England) · 2026Article
- Improving recombinant protein productivity in CHO cells via multi-omics data integration.Bioresources and bioprocessing · 2026Review
- Structural basis of lipid-dependent allosteric gating mechanisms for PC1-PC2 ion channel.Nature communications · 2026Article
- Reprogramming innate immunity through viral interference: A double-edged strategy for enhancing and containing gene therapies.Molecular therapy. Nucleic acids · 2026Review
- Predicting the translation efficiency of messenger RNA in mammalian cells.Nature biotechnology · 2026Article
- Beyond the Sequence: Chemical and Topological Design and Innovations in mRNA Therapeutics.Chemical reviews · 2026Review
- Designing 5' UTR sequences improves the capacity of mRNA therapeutics in preclinical models of aging and obesity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- UTR-DynaPro: a CNN-transformer multimodal language model for decoding 5'UTR regulatory mechanisms.Scientific reports · 2026Article
- CJ-1: an optimized mRNA platform with enhanced protein expression and minimal immunogenicity for therapeutic applications.Gene therapy · 2026Article
- Zero-shot benchmarking of RNA language models in structural, functional, and evolutionary learning.Briefings in bioinformatics · 2026Article
- A modular vaccine platform for optimized lipid nanoparticle mRNA immunogenicity.Nature biomedical engineering · 2026Article
- Structurally-optimised HPV16 E7/E6 mRNA-LPP mediates dose-sparing efficacy via tumour microenvironment reprogramming.Molecular biomedicine · 2026Article
- Accelerate the Highly Efficient Development of mRNA Vaccines Through Advanced Computational Methods.MedComm · 2026Review
- Circular mRNA against CleanCap linear mRNA vectors: comprehensive comparison, expression, active and passive immunization.Frontiers in immunology · 2026Article
- Targeting an essential viral oncoprotein with an IL-7-enhanced mRNA vaccine induces durable immunity to Merkel cell carcinoma.Cell reports · 2025Article
- Enhancing mRNA translation efficiency with discriminative and generative artificial intelligence by optimizing 5' UTR sequences.iScience · 2025Article
- A foundation language model to decipher diverse regulation of RNAs.Genome biology · 2025Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
Despite significant clinical progress in cell and gene therapies, maximizing protein expression in order to enhance potency remains a major technical challenge. Here, we develop a high-throughput strategy to design, screen, and optimize 5' UTRs that enhance protein expression from a strong human cytomegalovirus (CMV) promoter. We first identify naturally occurring 5' UTRs with high translation efficiencies and use this information with in silico genetic algorithms to generate synthetic 5' UTRs. A total of ~12,000 5' UTRs are then screened using a recombinase-mediated integration strategy that greatly enhances the sensitivity of high-throughput screens by eliminating copy number and position effects that limit lentiviral approaches. Using this approach, we identify three synthetic 5' UTRs that outperform commonly used non-viral gene therapy plasmids in expressing protein payloads. In summary, we demonstrate that high-throughput screening of 5' UTR libraries with recombinase-mediated integration can identify genetic elements that enhance protein expression, which should have numerous applications for engineered cell and gene therapies.
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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.