ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Generation of a hypomorphic model of propionic acidemia amenable to gene therapy testing.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 61 citations in OpenAlex.
- Propionic acidemia as a framework for understanding the impact of disturbed propionyl-CoA on histone modifications.Biochemical Society transactions · 2026Review
- Precision metabolic therapy for propionic acidemia.Biochemical pharmacology · 2026Review
- From N-of-1 to versatility in propionic acidemia: Antisense oligonucleotide-mediated skipping of a constitutiveMolecular therapy. Nucleic acids · 2026Article
- Loss of Propionyl-CoA Carboxylase Reprograms Hepatic Metabolism by Suppressing Mitochondrial Pyruvate Carboxylation and Fatty Acid Oxidation.bioRxiv : the preprint server for biology · 2026Article
- Generation of an isogenic human induced pluripotent stem cell line with a mutant propionyl-CoA carboxylase α subunit.Orphanet journal of rare diseases · 2026Article
- H4K16 acylations destabilize chromatin architecture and facilitate transcriptional response during metabolic perturbations.Molecular cell · 2026Article
- Propionic Acidemia-Induced Proarrhythmic Electrophysiological Alterations in Human iPSC-Derived Cardiomyocytes.Journal of inherited metabolic disease · 2025Article
- Metabolic flux analysis in hiPSC-CMs reveals insights into cardiac dysfunction in propionic acidemia.Cellular and molecular life sciences : CMLS · 2025Article
- Renal phenotyping in a hypomorphic murine model of propionic aciduria reveals common pathomechanisms in organic acidurias.Scientific reports · 2024Article
- The attenuated hepatic clearance of propionate increases cardiac oxidative stress in propionic acidemia.Basic research in cardiology · 2024Article
- Crossing epigenetic frontiers: the intersection of novel histone modifications and diseases.Signal transduction and targeted therapy · 2024Review
- Fasting alleviates metabolic alterations in mice with propionyl-CoA carboxylase deficiency due to Pcca mutation.Communications biology · 2024Article
- Characterizing the mechanism of action for mRNA therapeutics for the treatment of propionic acidemia, methylmalonic acidemia, and phenylketonuria.Nature communications · 2024Article
- RegulatingMolecular therapy. Nucleic acids · 2024Article
- Disrupted propionate metabolism evokes transcriptional changes in the heart by increasing histone acetylation and propionylation.Nature cardiovascular research · 2023Article
- Studying a propionic acidaemia mouse model reveals epigenetic mechanisms in the heart.Nature cardiovascular research · 2023Article
- Systemic gene therapy using an AAV44.9 vector rescues a neonatal lethal mouse model of propionic acidemia.Molecular therapy. Methods & clinical development · 2023Article
- Pathophysiological mechanisms of complications associated with propionic acidemia.Pharmacology & therapeutics · 2023Review
- Review
- Dysregulated Cell Homeostasis and miRNAs in Human iPSC-Derived Cardiomyocytes from a Propionic Acidemia Patient with Cardiomyopathy.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Propionic acidemia (PA) is a recessive genetic disease that results in an inability to metabolize certain amino acids and odd-chain fatty acids. Current treatment involves restricting consumption of these substrates or liver transplantation. Deletion of the Pcca gene in mice mimics the most severe forms of the human disease. Pcca(-) mice die within 36 hours of birth, making it difficult to test intravenous systemic therapies in them. We generated an adult hypomorphic model of PA in Pcca(-) mice using a transgene bearing an A138T mutant of the human PCCA protein. Pcca(-/-)(A138T) mice have 2% of wild-type PCC activity, survive to adulthood, and have elevations in propionyl-carnitine, methylcitrate, glycine, alanine, lysine, ammonia, and markers associated with cardiomyopathy similar to those in patients with PA. This adult model allowed gene therapy testing by intravenous injection with adenovirus serotype 5 (Ad5) and adeno-associated virus 2/8 (AAV8) vectors. Ad5-mediated more rapid increases in PCCA protein and propionyl-CoA carboxylase (PCC) activity in the liver than AAV8 and both vectors reduced propionylcarnitine and methylcitrate levels. Phenotypic correction was transient with first generation Ad whereas AAV8-mediated long-lasting effects. These data suggest that this PA model may be a useful platform for optimizing systemic intravenous therapies for PA.
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