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Full-Text Articles in Emergency Medicine
Long-Term Correction Of Ornithine Transcarbamylase Deficiency By Wpre-Mediated Overexpression Using A Helper-Dependent Adenovirus, Asad Mian, W. Michael Mccormack Jr, Viraj Mane, Soledad Kleppe, Philip Ng, Milton Finegold, William E. O'Brien, John R. Rodgers, Arthur L. Beaude, Brendan Lee
Long-Term Correction Of Ornithine Transcarbamylase Deficiency By Wpre-Mediated Overexpression Using A Helper-Dependent Adenovirus, Asad Mian, W. Michael Mccormack Jr, Viraj Mane, Soledad Kleppe, Philip Ng, Milton Finegold, William E. O'Brien, John R. Rodgers, Arthur L. Beaude, Brendan Lee
Department of Emergency Medicine
The urea cycle disorders (UCDs) are important models for developing gene replacement therapy for liver diseases. Long-term correction of the most common UCD, ornithine transcarbamylase (OTC) deficiency, has yet to be achieved in clinical or preclinical settings. The single human clinical trial using early-generation adenovirus (Ad) failed to show any biochemical correction. In adult OTC-deficient mice, an E1/E2-deleted Ad vector expressing the mouse OTC gene, but not the human, was only transiently therapeutic. By using post-transcriptional overexpression in the context of the less immunogenic helper-dependent adenoviral vector, we achieved metabolic correction of adult OTC-deficient mice for >6 months. Demonstrating this …