ArticleNucleic acids research2022
Translational enhancement by base editing of the Kozak sequence rescues haploinsufficiency.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Article
- Kozak sequence libraries for systematically characterizing transgenes across expression levels.Nucleic acids research · 2026Article
- Kozak sequences regulate gene expression in Trypanosoma brucei.Nucleic acids research · 2026Article
- Recent Progress in Sequence Optimization of mRNA Vaccine: Biological Mechanism, Quantitative Metrics, and Computational Model.Bioinformatics and biology insights · 2026Review
- An effective method to enhance transient gene expression by transfecting high-density CHO cells.AMB Express · 2025Article
- Translational regulation of PKD1 by evolutionarily conserved upstream open reading frames.RNA biology · 2025Review
- AUGcontext DB: a comprehensive catalog of the mRNA AUG initiator codon context across eukaryotes.RNA biology · 2025Review
- A Cornelia de Lange syndrome NIPBL 5'-UTR mutation reduces cell proliferation in anBiomedical reports · 2025Article
- Cryptic intronic transcriptional initiation generates efficient endogenous mRNA templates for C9orf72-associated RAN translation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Kv3.3 Expression Enhanced by a Novel Variant in the Kozak Sequence ofInternational journal of molecular sciences · 2024Article
- Optimization of a novel expression system for recombinant protein production in CHO cells.Scientific reports · 2024Article
- Host-dependent C-to-U RNA editing in SARS-CoV-2 creates novel viral genes with optimized expressibility.Frontiers in cellular and infection microbiology · 2024Article
- Precise genome editing of the Kozak sequence enables bidirectional and quantitative modulation of protein translation to anticipated levels without affecting transcription.Nucleic acids research · 2023Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
A variety of single-gene human diseases are caused by haploinsufficiency, a genetic condition by which mutational inactivation of one allele leads to reduced protein levels and functional impairment. Translational enhancement of the spare allele could exert a therapeutic effect. Here we developed BOOST, a novel gene-editing approach to rescue haploinsufficiency loci by the change of specific single nucleotides in the Kozak sequence, which controls translation by regulating start codon recognition. We evaluated for translational strength 230 Kozak sequences of annotated human haploinsufficient genes and 4621 derived variants, which can be installed by base editing, by a high-throughput reporter assay. Of these variants, 149 increased the translation of 47 Kozak sequences, demonstrating that a substantial proportion of haploinsufficient genes are controlled by suboptimal Kozak sequences. Validation of 18 variants for 8 genes produced an average enhancement in an expression window compatible with the rescue of the genetic imbalance. Base editing of the NCF1 gene, whose monoallelic loss causes chronic granulomatous disease, resulted in the desired increase of NCF1 (p47phox) protein levels in a relevant cell model. We propose BOOST as a fine-tuned approach to modulate translation, applicable to the correction of dozens of haploinsufficient monogenic disorders independently of the causing mutation.
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