ArticleMolecular therapy. Nucleic acids2017
Low-Dose Gene Therapy for Murine PKU Using Episomal Naked DNA Vectors Expressing PAH from Its Endogenous Liver Promoter.
Article in Molecular therapy. Nucleic acids, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
16 citing papers in PubMed, 22 citations in OpenAlex.
- Minicircle DNA Vaccines: Overcoming Delivery and Expression Barriers in Next-Generation Immunization.Vaccines · 2026Review
- Progress and prospect of minicircle as a minimized non-viral DNA vector in gene therapy and regenerative medicine.Molecular therapy. Nucleic acids · 2025Review
- Experimental Galactose-1-Phosphate Uridylyltransferase (GALT) mRNA Therapy Improves Motor-Related Phenotypes in a Mouse Model of Classic Galactosemia-A Pilot Study.Biomedicines · 2025Article
- Therapeutic liver cell transplantation to treat murine PKU.Journal of inherited metabolic disease · 2024Article
- Continuous directed evolution of a compact CjCas9 variant with broad PAM compatibility.Nature chemical biology · 2024Article
- State-of-the-art 2023 on gene therapy for phenylketonuria.Journal of inherited metabolic disease · 2024Review
- Intrabiliary infusion of naked DNA vectors targets periportal hepatocytes in mice.Molecular therapy. Methods & clinical development · 2022Article
- Enhanced genome editing to ameliorate a genetic metabolic liver disease through co-delivery of adeno-associated virus receptor.Science China. Life sciences · 2022Article
- In vivo prime editing of a metabolic liver disease in mice.Science translational medicine · 2022Article
- Delivery of non-viral naked DNA vectors to liver in small weaned pigs by hydrodynamic retrograde intrabiliary injection.Molecular therapy. Methods & clinical development · 2022Article
- Single-molecule long-read sequencing reveals the potential impact of posttranscriptional regulation on gene dosage effects on the avian Z chromosome.BMC genomics · 2022Article
- Development of Covalent Chitosan-Polyethylenimine Derivatives as Gene Delivery Vehicle: Synthesis, Characterization, and Evaluation.International journal of molecular sciences · 2021Article
- A novel Pah-exon1 deleted murine model of phenylalanine hydroxylase (PAH) deficiency.Molecular genetics and metabolism · 2020Article
- State-of-the-Art 2019 on Gene Therapy for Phenylketonuria.Human gene therapy · 2019Review
- Review
- Technical Improvement and Application of Hydrodynamic Gene Delivery in Study of Liver Diseases.Frontiers in pharmacology · 2017Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Limited duration of transgene expression, insertional mutagenesis, and size limitations for transgene cassettes pose challenges and risk factors for many gene therapy vectors. Here, we report on physiological expression of liver phenylalanine hydroxylase (PAH) by delivery of naked DNA/minicircle (MC)-based vectors for correction of homozygous enu2 mice, a model of human phenylketonuria (PKU). Because MC vectors lack a defined size limit, we constructed a MC vector expressing a codon-optimized murine Pah cDNA that includes a truncated intron and is under the transcriptional control of a 3.6-kb native Pah promoter/enhancer sequence. This vector, delivered via hydrodynamic injection, yielded therapeutic liver PAH activity and sustained correction of blood phenylalanine comparable to viral or synthetic liver promoters. Therapeutic efficacy was seen with vector copy numbers of <1 vector genome per diploid hepatocyte genome and was achieved at a vector dose that was significantly lowered. Partial hepatectomy and subsequent liver regeneration was associated with >95% loss of vector genomes and PAH activity in liver, demonstrating that MC vectors had not integrated into the liver genome. In conclusion, MC vectors, which do not have a defined size-limitation, offer a favorable safety profile for hepatic gene therapy due to their non-integration in combination with native promoters.
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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.