ArticleGene therapy2012
Sustained correction of OTC deficiency in spf( ash) mice using optimized self-complementary AAV2/8 vectors.
Article in Gene therapy, 2012. 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, 41 citations in OpenAlex.
- Review
- Characterization of a novel conditional knockout mouse model to assess efficacy of mRNA therapy in the context of severe OTC deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Gender difference in pre-clinical liver-directed gene therapy with lentiviral vectors.Experimental biology and medicine (Maywood, N.J.) · 2025Article
- Lipid nanoparticle-targeted mRNA formulation as a treatment for ornithine-transcarbamylase deficiency model mice.Molecular therapy. Nucleic acids · 2023Article
- Genetic Therapy Approaches for Ornithine Transcarbamylase Deficiency.Biomedicines · 2023Review
- Hyperammonemia in Inherited Metabolic Diseases.Cellular and molecular neurobiology · 2022Review
- The LOX-1 receptor ectopically expressed in the liver alleviates atherosclerosis by clearing Ox-LDL from the circulation.Molecular medicine (Cambridge, Mass.) · 2022Article
- OTC intron 4 variations mediate pathogenic splicing patterns caused by the c.386G>A mutation in humans and spfMolecular medicine (Cambridge, Mass.) · 2021Article
- Developing a second-generation clinical candidate AAV vector for gene therapy of familial hypercholesterolemia.Molecular therapy. Methods & clinical development · 2021Article
- Long-term correction of ornithine transcarbamylase deficiency in Spf-Ash mice with a translationally optimized AAV vector.Molecular therapy. Methods & clinical development · 2021Article
- Gene delivery corrects N-acetylglutamate synthase deficiency and enables insights in the physiological impact of L-arginine activation of N-acetylglutamate synthase.Scientific reports · 2021Article
- A mutation-independent CRISPR-Cas9-mediated gene targeting approach to treat a murine model of ornithine transcarbamylase deficiency.Science advances · 2020Article
- AAV8 Gene Therapy for Crigler-Najjar Syndrome in Macaques Elicited Transgene T Cell Responses That Are Resident to the Liver.Molecular therapy. Methods & clinical development · 2018Article
- AAV gene therapy corrects OTC deficiency and prevents liver fibrosis in aged OTC-knock out heterozygous mice.Molecular genetics and metabolism · 2017Article
- Effects of Self-Complementarity, Codon Optimization, Transgene, and Dose on Liver Transduction with AAV8.Human gene therapy methods · 2016Article
- Emerging therapies for mitochondrial disorders.Brain : a journal of neurology · 2016Review
- A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice.Nature biotechnology · 2016Article
- Progresses towards safe and efficient gene therapy vectors.Oncotarget · 2015Review
- Article
- Kinetics of adeno-associated virus serotype 2 (AAV2) and AAV8 capsid antigen presentation in vivo are identical.Human gene therapy · 2013Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Ornithine transcarbamylase deficiency (OTCD) is the most common inborn error of urea synthesis. Complete OTCD can result in hyperammonemic coma in the neonatal period, which can rapidly become fatal. Current acute therapy involves dialysis; chronic therapy involves the stimulation of alternate nitrogen clearance pathways; and the only curative approach is liver transplantation. Adeno-associated virus (AAV) vector-based gene therapy would add to current treatment options provided the vector delivers high level and stable transgene expression in liver without dose-limiting toxicity. In this study, we employed an AAV2/8-based self-complementary (sc) vector expressing the murine OTC (mOTC) gene under a liver-specific thyroxine-binding globulin promoter and examined the therapeutic effects in a mouse model of OTCD, the spf (ash) mouse. Seven days after a single intravenous injection of vector, treated mice showed complete normalization of urinary orotic acid, a measure of OTC activity. We further improved vector efficacy by incorporating a Kozak or Kozak-like sequence into mOTC complementary DNA, which increased the OTC activity by five or twofold and achieved sustained correction of orotic aciduria for up to 7 months. Our results demonstrate that vector optimizations can significantly improve the efficacy of gene therapy.
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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.