ArticleHuman gene therapy2010
Liver-directed recombinant adeno-associated viral gene delivery rescues a lethal mouse model of methylmalonic acidemia and provides long-term phenotypic correction.
Article in Human gene therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 53 citations in OpenAlex.
- Targeting proximal tubule mitochondrial dysfunction attenuates the renal disease of methylmalonic acidemia.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- Rab1A Promotes Hepatic Steatosis by Suppressing Mitophagy via the Raf-1/ERK1/2/PINK1 Signaling Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Systemic gene therapy using an AAV44.9 vector rescues a neonatal lethal mouse model of propionic acidemia.Molecular therapy. Methods & clinical development · 2023Article
- Administration of Glutaredoxin-1 Attenuates Liver Fibrosis Caused by Aging and Non-Alcoholic Steatohepatitis.Antioxidants (Basel, Switzerland) · 2022Article
- Novel AAV-mediated genome editing therapy improves health and survival in a mouse model of methylmalonic acidemia.PloS one · 2022Article
- Article
- Mitochondrial disease, mitophagy, and cellular distress in methylmalonic acidemia.Cellular and molecular life sciences : CMLS · 2021Review
- MicroRNA-497 induced by Clonorchis sinensis enhances the TGF-β/Smad signaling pathway to promote hepatic fibrosis by targeting Smad7.Parasites & vectors · 2021Article
- ImmTOR nanoparticles enhance AAV transgene expression after initial and repeat dosing in a mouse model of methylmalonic acidemia.Molecular therapy. Methods & clinical development · 2021Article
- Central nervous system-targeted adeno-associated virus gene therapy in methylmalonic acidemia.Molecular therapy. Methods & clinical development · 2021Article
- Promoterless, Nuclease-Free Genome Editing Confers a Growth Advantage for Corrected Hepatocytes in Mice With Methylmalonic Acidemia.Hepatology (Baltimore, Md.) · 2021Article
- Chemical modification of the adeno-associated virus capsid to improve gene delivery.Chemical science · 2019Article
- Gene Therapy for Methylmalonic Acidemia: Past, Present, and Future.Human gene therapy · 2019Review
- Systemic Messenger RNA Therapy as a Treatment for Methylmalonic Acidemia.Cell reports · 2017Article
- Non-cell-autonomous activation of IL-6/STAT3 signaling mediates FGF19-driven hepatocarcinogenesis.Nature communications · 2017Article
- Improving lipoprotein profiles by liver-directed gene transfer of low density lipoprotein receptor gene in hypercholesterolaemia mice.Journal of genetics · 2016Article
- Neutralizing Antibodies Against Adeno-Associated Viral Capsids in Patients with mut Methylmalonic Acidemia.Human gene therapy · 2016Article
- Vector design influences hepatic genotoxicity after adeno-associated virus gene therapy.The Journal of clinical investigation · 2015Article
- Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia.Orphanet journal of rare diseases · 2014Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Methylmalonic acidemia is a severe metabolic disorder caused by a deficiency of the ubiquitously expressed mitochondrial enzyme, methylmalonyl-CoA mutase (MUT). Liver transplantation has been used to treat a small number of patients with variable success, and whether liver-directed gene therapy might be employed in such a pleiotropic metabolic disorder is uncertain. In this study, we examined the therapeutic effects of hepatocyte-directed delivery of the Mut gene to mice with a severe form of methylmalonic acidemia. We show that a single intrahepatic injection of recombinant adeno-associated virus serotype 8 expressing the Mut gene under the control of the liver-specific thyroxine-binding globulin (TBG) promoter is sufficient to rescue Mut(-/-) mice from neonatal lethality and provide long-term phenotypic correction. Treated Mut(-/-) mice lived beyond 1 year of age, had improved growth, lower plasma methylmalonic acid levels, and an increased capacity to oxidize [1-(13)C]propionate in vivo. The older treated mice showed increased Mut transcription, presumably mediated by upregulation of the TBG promoter during senescence. The results indicate that the stable transduction of a small number of hepatocytes with the Mut gene can be efficacious in the phenotypic correction of an inborn error of organic acid metabolism and support the rapid translation of liver-directed gene therapy vectors already optimized for human subjects to patients with methylmalonic acidemia.
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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.