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Full-Text Articles in Medicine and Health Sciences
Long-Term Correction Of Very Long-Chain Acyl-Coa Dehydrogenase Deficiency In Mice Using Aav9 Gene Therapy, Allison Keeler, Thomas Conlon, Glenn Walter, Huadong Zeng, Scott Shaffer, Fu Dungtao, Kirsten Erger, Travis Cossette, Qiushi Tang, Christian Mueller, Terence Flotte
Long-Term Correction Of Very Long-Chain Acyl-Coa Dehydrogenase Deficiency In Mice Using Aav9 Gene Therapy, Allison Keeler, Thomas Conlon, Glenn Walter, Huadong Zeng, Scott Shaffer, Fu Dungtao, Kirsten Erger, Travis Cossette, Qiushi Tang, Christian Mueller, Terence Flotte
Christian Mueller
Very long-chain acyl-coA dehydrogenase (VLCAD) is the rate-limiting step in mitochondrial fatty acid oxidation. VLCAD-deficient mice and patients clinical symptoms stem from not only an energy deficiency but also long-chain metabolite accumulations. VLCAD-deficient mice were treated systemically with 1 x 10(12) vector genomes of recombinant adeno-associated virus 9 (rAAV9)-VLCAD. Biochemical correction was observed in vector-treated mice beginning 2 weeks postinjection, as characterized by a significant drop in long-chain fatty acyl accumulates in whole blood after an overnight fast. Changes persisted through the termination point around 20 weeks postinjection. Magnetic resonance spectroscopy (MRS) and tandem mass spectrometry (MS/MS) revealed normalization of …
Gene Transfer In The Lung Using Recombinant Adeno-Associated Virus, Alisha Gruntman, Christian Mueller, Terence Flotte, Guangping Gao
Gene Transfer In The Lung Using Recombinant Adeno-Associated Virus, Alisha Gruntman, Christian Mueller, Terence Flotte, Guangping Gao
Christian Mueller
Adeno-associated virus (AAV) is a small replication-deficient DNA virus belonging to the Parvovirinae family. It has a single-stranded ∼4.7-kb genome. Recombinant AAV (rAAV) is created by replacing the viral rep and cap genes with the transgene of interest along with promoter and polyadenylation sequences. The short viral inverted terminal repeats must remain intact for replication and packaging in production, as well as vector genome processing and persistence in the transduction process. The AAV capsid (serotype) determines the tissue tropism of the rAAV vector. In this unit we will discuss serotype selection for lung targeting along with the factors effecting efficient …
Raav9 Airway Delivery Results In Effective Knockdown Of Mutant Alpha 1-Antitrypsin In The Liver While Upregulating Wildtype Alpha 1-Antitrypsin In The Lung, Alisha Gruntman, Christian Mueller, Qiushi Tang, Lina Song, James M. Wilson, Terence R. Flotte, Maria P. Limberis
Raav9 Airway Delivery Results In Effective Knockdown Of Mutant Alpha 1-Antitrypsin In The Liver While Upregulating Wildtype Alpha 1-Antitrypsin In The Lung, Alisha Gruntman, Christian Mueller, Qiushi Tang, Lina Song, James M. Wilson, Terence R. Flotte, Maria P. Limberis
Christian Mueller
Alpha 1-Antitrypsin (AAT) deficiency is a human genetic disease resulting in the production of mutant AAT, a hepatocyte produced serine protease inhibitor that functions to prevent alveolar epithelial damage by inhibiting neutrophil elastase. Patients with AAT deficiency have increased lung disease, due to decreased proteolytic protection, as well as sporadic severe liver disease secondary to accumulation of mutant AAT, especially a common mutant form termed PiZ, within hepatocytes. We previously showed, in a PiZ mutant mouse model, simultaneous knock-down of mutant PiZ-AAT and augmentation of wild-type AAT production through intravenous delivery of a recombinant adeno-associated viral (rAAV) vector encoding both …