Journal article

Correction of Methylmalonic Aciduria In Vivo Using a Codon-Optimized Lentiviral Vector

Edward SY Wong, Chantelle McIntyre, Heidi L Peters, Enzo Ranieri, Donald S Anson, Janice M Fletcher

Human Gene Therapy | MARY ANN LIEBERT, INC | Published : 2014


Methylmalonic aciduria is a rare disorder of organic acid metabolism with limited therapeutic options, resulting in high morbidity and mortality. Positive results from combined liver/kidney transplantation suggest, however, that metabolic sink therapy may be efficacious. Gene therapy offers a more accessible approach for the treatment of methylmalonic aciduria than organ transplantation. Accordingly, we have evaluated a lentiviral vector-mediated gene transfer approach in an in vivo mouse model of methylmalonic aciduria. A mouse model of methylmalonic aciduria (Mut(-/-)MUT(h2)) was injected intravenously at 8 weeks of age with a lentiviral vector that expressed a codon-optimized human methyl..

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Funding Acknowledgements

This work was supported by funding from the Women's and Children's Hospital Foundation and the Australian National Health and Medical Research Council. The authors would like to thank Dr. Nicole Buck for providing assistance with the mouse model; Dr. David Johnson, Rosemarie Gerace, and Minh-Uyen Trinh for technical assistance with biochemical analyses; Dr. Peter Clements for technical support with the HPLC experiments; and Lynn Marsden for her assistance with animal sampling procedures.