ArticleHGG advances2024
A base editing strategy using mRNA-LNPs for in vivo correction of the most frequent phenylketonuria variant.
Article in HGG advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Improved specificity and efficiency of in vivo adenine base editing therapies with hybrid guide RNAs.Nature biomedical engineering · 2026Article
- Review
- Efficient prime editing in vivo and in vitro using lipid nanoparticles.Nature nanotechnology · 2026Article
- sgRNA amount is a limiting factor in adenine base editing using RNA LNPs.Molecular therapy. Nucleic acids · 2026Article
- Article
- Implications of the FDA's new plausible mechanism framework for the development of a personalized in vivo prime editing platform.American journal of human genetics · 2026Review
- Correction of a recurrent pathogenic variant in methylmalonic acidemia using adenine base editing.bioRxiv : the preprint server for biology · 2026Article
- Balancing personalized medicine and scalability in base editing for phenylketonuria.Molecular therapy. Nucleic acids · 2026Article
- Review
- Lipid Nanoparticles for Delivery of CRISPR Gene Editing Components.Small methods · 2026Review
- Base editing strategies forMolecular therapy. Nucleic acids · 2025Article
- In vivo base editing reduces liver cysts in autosomal dominant polycystic kidney disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Treatment of a metabolic liver disease in mice with a transient prime editing approach.Nature biomedical engineering · 2025Article
- Review
- Advancing Gene Therapy for Phenylketonuria: From Precision Editing to Clinical Translation.International journal of molecular sciences · 2025Review
- Review
- CRISPR-Cas technologies: Emerging tools from research to clinical application.Journal of microbiology (Seoul, Korea) · 2025Review
- CRISPR/Cas9 Delivery Systems to Enhance Gene Editing Efficiency.International journal of molecular sciences · 2025Review
- Advanced delivery systems for gene editing: A comprehensive review from the GenE-HumDi COST Action Working Group.Molecular therapy. Nucleic acids · 2025Review
- Efficient and safe in vivo treatment of primary hyperoxaluria type 1 via LNP-CRISPR-Cas9-mediated glycolate oxidase disruption.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
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9 authors.
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Abstract
The c.1222C>T (p.Arg408Trp) phenylalanine hydroxylase (PAH) variant is the most frequent cause of phenylketonuria (PKU), an autosomal recessive disorder characterized by accumulation of blood phenylalanine (Phe) to neurotoxic levels. Here we devised a therapeutic base editing strategy to correct the variant, using prime-edited hepatocyte cell lines engineered with the c.1222C>T variant to screen a variety of adenine base editors and guide RNAs in vitro, followed by assessment in c.1222C>T humanized mice in vivo. We found that upon delivery of a selected adenine base editor mRNA/guide RNA combination into mice via lipid nanoparticles (LNPs), there was sufficient PAH editing in the liver to fully normalize blood Phe levels within 48 h. This work establishes the viability of a base editing strategy to correct the most common pathogenic variant found in individuals with the most common inborn error of metabolism, albeit with potential limitations compared with other genome editing approaches.
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