Pre-clinical efficacy and dosing of an AAV8 vector expressing human methylmalonyl-CoA mutase in a murine model of methylmalonic acidemia (MMA)
RJ Chandler, CP Venditti - Molecular genetics and metabolism, 2012 - Elsevier
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.
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.