title: Pre-clinical efficacy and dosing of an AAV8 vector expressing human methylmalonyl-CoA mutase in a murine model of methylmalonic acidemia (MMA).
abstract: We demonstrate that human methylmalonyl-CoA mutase (MUT), delivered using an AAV serotype 8 vector, rescues the lethal phenotype displayed by mice with MMA and provides long-term phenotypic correction. In addition to defining a lower limit of effective dosing, our studies establish that neither a species barrier to mitochondrial processing nor an apparent immune response to MUT limits the murine model as an experimental platform to test the efficacy of human gene therapy vectors for MMA.
authors.affiliation: Organic Acid Research Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Chandler
authors.forename: Charles P
authors.initials: CP
authors.lastname: Venditti
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000595:Amino Acid Sequence; D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008765:Methylmalonyl-CoA Mutase / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010641:Phenotype; D016415:Sequence Alignment; D015996:Survival Rate
chemical_list: D008765:Methylmalonyl-CoA Mutase