ArticleAmerican journal of human genetics2023
Efficient in vivo prime editing corrects the most frequent phenylketonuria variant, associated with high unmet medical need.
Article in American journal of human genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Pooled it
- Dense RNA motif modifications enable robust in vivo prime editing and enhance efficiencies of diverse editing systems.Nature biomedical engineering · 2026Article
- Review
- Efficient prime editing in vivo and in vitro using lipid nanoparticles.Nature nanotechnology · 2026Article
- Article
- A primer on prime: A prime editing update from advances to first-in-human trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Directed evolution of small RNA-stabilizing motifs that improve prime-editing efficiency.Nature biotechnology · 2026Article
- 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
- Non-viral delivery of genome-editing tools for treatment of genetic disorders.Acta pharmaceutica Sinica. B · 2026Review
- CRISPR-Cas9 Therapeutics in Early Clinical Development: Delivery and Molecular Diagnostics.Cells · 2026Review
- Balancing personalized medicine and scalability in base editing for phenylketonuria.Molecular therapy. Nucleic acids · 2026Article
- Two Years of Expanded Newborn Screening in Russia: High-Throughput Detection of Inherited Metabolic Disorders by Tandem Mass Spectrometry with Next-Generation Sequencing Confirmation.International journal of neonatal screening · 2026Article
- Prime editing in mammals: From promise to practicalities.Molecular therapy. Nucleic acids · 2025Review
- Base editing strategies forMolecular therapy. Nucleic acids · 2025Article
- Synthetic closed-loop gene circuit for phenylalanine regulation.Nucleic acids research · 2025Article
- Treatment of a metabolic liver disease in mice with a transient prime editing approach.Nature biomedical engineering · 2025Article
- Advancing Gene Therapy for Phenylketonuria: From Precision Editing to Clinical Translation.International journal of molecular sciences · 2025Review
- Article
- Advancements in CRISPR/Cas systems for disease treatment.Acta pharmaceutica Sinica. B · 2025Review
- Experimental Animal Models of Phenylketonuria: Pros and Cons.International journal of molecular sciences · 2025Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The c.1222C>T (p.Arg408Trp) variant in the phenylalanine hydroxylase gene (PAH) is the most frequent cause of phenylketonuria (PKU), the most common inborn error of metabolism. This autosomal-recessive disorder is characterized by accumulation of blood phenylalanine (Phe) to neurotoxic levels. Using real-world data, we observed that despite dietary and medical interventions, most PKU individuals harboring at least one c.1222C>T variant experience chronic, severe Phe elevations and do not comply with Phe monitoring guidelines. Motivated by these findings, we generated an edited c.1222C>T hepatocyte cell line and humanized c.1222C>T mouse models, with which we demonstrated efficient in vitro and in vivo correction of the variant with prime editing. Delivery via adeno-associated viral (AAV) vectors reproducibly achieved complete normalization of blood Phe levels in PKU mice, with up to 52% whole-liver corrective PAH editing. These studies validate a strategy involving prime editing as a potential treatment for a large proportion of individuals with PKU.
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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.