ArticleNature biotechnology2026
Prime editor-based high-throughput screening reveals functional synonymous mutations in human cells.
Article in Nature biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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.
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Who cites it
11 citing papers in PubMed.
- Advances in prime editing: Molecular innovations, Large-fragment engineering, and AI-driven design.Biodesign research · 2026Review
- Compound delivery of eVLPs enhances prime editing for targeted genome engineering and high-throughput screening.Cell genomics · 2026Article
- eVLP compound delivery breaks the prime editing efficiency ceiling.Cell genomics · 2026Article
- Synonymous mutations in essential genes infrequently produce fitness effects in human cell lines.Nucleic acids research · 2026Article
- Pervasive relaxed selection on spermatogenesis genes coincident with the evolution of polygyny in gorillas.eLife · 2026Article
- Pangolin museum genomics reveal the dynamic genetic consequences and extinction risk of the critically endangered Chinese pangolin.Molecular biology and evolution · 2026Article
- CDsyn: A comprehensive database for deleterious human synonymous variation prediction.iScience · 2026Article
- Uncovering evolutionary and phylogenetic relationships in Glyptothorax species through comparative mitochondrial genomics.Journal, genetic engineering & biotechnology · 2026Article
- Synonymous Variants of Potential Significance Identified by a 52-Gene Clinical Sequencing Panel in Non-Small Cell Lung Cancer.Genes, chromosomes & cancer · 2026Article
- TPdsm: a method based on TabPFN for prediction of deleterious synonymous mutations.Bioinformatics advances · 2026Article
- High-throughput screening of human genetic variants by pooled prime editing.Cell genomics · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Synonymous mutations are generally considered neutral, while their roles in the human genome remain largely unexplored. Here we use the PEmax system to create a library of 297,900 engineered prime-editing guide RNAs and perform extensive screening to identify synonymous mutations affecting cell fitness. Unlike recent findings in yeast, group-level analyses show that synonymous mutations diverge from nonsynonymous mutations in fitness effects yet exhibit similar phenotypic distributions relative to negative controls. Following rigorous quality control, only a small subset demonstrated measurable effects. For these functional mutations, we develop a specialized machine learning tool and uncover their impact on various biological processes such as messenger RNA splicing and transcription, supported by multifaceted experimental evidence. We find that synonymous mutations can alter RNA folding and affect translation, as demonstrated by PLK1_S2. By integrating screening data with our model, we predict clinically deleterious synonymous mutations. This research deepens our understanding of synonymous mutations, providing insights for clinical disease studies.
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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.