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Articles 1 - 3 of 3
Full-Text Articles in Genetics and Genomics
5 Year Expression And Neutrophil Defect Repair After Gene Therapy In Alpha-1 Antitrypsin Deficiency, Christian Mueller, Gwladys Gernoux, Alisha M. Gruntman, Florie Borel, Emer P. Reeves, Roberto Calcedo, Farshid N. Rouhani, Anthony Yachnis, Margaret Humphries, Martha Campbell-Thompson, Louis M. Messina, Jeffrey D. Chulay, Bruce Trapnell, James M. Wilson, Noel G. Mcelvaney, Terence R. Flotte
5 Year Expression And Neutrophil Defect Repair After Gene Therapy In Alpha-1 Antitrypsin Deficiency, Christian Mueller, Gwladys Gernoux, Alisha M. Gruntman, Florie Borel, Emer P. Reeves, Roberto Calcedo, Farshid N. Rouhani, Anthony Yachnis, Margaret Humphries, Martha Campbell-Thompson, Louis M. Messina, Jeffrey D. Chulay, Bruce Trapnell, James M. Wilson, Noel G. Mcelvaney, Terence R. Flotte
Christian Mueller
Alpha-1 antitrypsin deficiency is a monogenic disorder resulting in emphysema due principally to the unopposed effects of neutrophil elastase. We previously reported achieving plasma wild-type alpha-1 antitrypsin concentrations at 2.5%-3.8% of the purported therapeutic level at 1 year after a single intramuscular administration of recombinant adeno-associated virus serotype 1 alpha-1 antitrypsin vector in alpha-1 antitrypsin deficient patients. We analyzed blood and muscle for alpha-1 antitrypsin expression and immune cell response. We also assayed previously reported markers of neutrophil function known to be altered in alpha-1 antitrypsin deficient patients. Here, we report sustained expression at 2.0%-2.5% of the target level from …
Human Treg Responses Allow Sustained Recombinant Adeno-Associated Virus-Mediated Transgene Expression, Christian Mueller, Jeffrey Chulay, Bruce Trapnell, Margaret Humphries, Brenna Carey, Robert Sandhaus, Noel Mcelvaney, Louis Messina, Qiushi Tang, Farshid Rouhani, Martha Campbell-Thompson, Ann Fu, Anthony Yachnis, David Knop, Guo-Jie Ye, Mark Brantly, Roberto Calcedo, Suryanarayan Somanathan, Lee Richman, Robert Vonderheide, Maigan Hulme, Todd Brusko, James Wilson, Terence Flotte
Human Treg Responses Allow Sustained Recombinant Adeno-Associated Virus-Mediated Transgene Expression, Christian Mueller, Jeffrey Chulay, Bruce Trapnell, Margaret Humphries, Brenna Carey, Robert Sandhaus, Noel Mcelvaney, Louis Messina, Qiushi Tang, Farshid Rouhani, Martha Campbell-Thompson, Ann Fu, Anthony Yachnis, David Knop, Guo-Jie Ye, Mark Brantly, Roberto Calcedo, Suryanarayan Somanathan, Lee Richman, Robert Vonderheide, Maigan Hulme, Todd Brusko, James Wilson, Terence Flotte
Christian Mueller
Recombinant adeno-associated virus (rAAV) vectors have shown promise for the treatment of several diseases; however, immune-mediated elimination of transduced cells has been suggested to limit and account for a loss of efficacy. To determine whether rAAV vector expression can persist long term, we administered rAAV vectors expressing normal, M-type alpha-1 antitrypsin (M-AAT) to AAT-deficient subjects at various doses by multiple i.m. injections. M-specific AAT expression was observed in all subjects in a dose-dependent manner and was sustained for more than 1 year in the absence of immune suppression. Muscle biopsies at 1 year had sustained AAT expression and a reduction …
Modulation Of Exaggerated-Ige Allergic Responses By Gene Transfer-Mediated Antagonism Of Il-13 And Il-17e., Christian Mueller, Allison Keeler, Sofia Braag, Timothy Menz, Qiushi Tang, Terence Flotte
Modulation Of Exaggerated-Ige Allergic Responses By Gene Transfer-Mediated Antagonism Of Il-13 And Il-17e., Christian Mueller, Allison Keeler, Sofia Braag, Timothy Menz, Qiushi Tang, Terence Flotte
Christian Mueller
Asthma and allergic rhinitis are almost invariable accompanied by elevated levels of immunoglobin E (IgE), and more importantly a genetic link between IgE levels and airway hyper-responsiveness has been established. We hypothesized that expression of soluble receptors directed against interleukin (IL)-13 and IL-17e would prevent the cytokines from engaging the cell-bound receptors and therefore help to attenuate allergic responses in a Cftr(-/-)-dependent mouse model of exaggerated-IgE responses. Cftr(-/-) mice were injected with recombinant adeno-associated virus 1 (rAAV1) intramuscularly expressing soluble receptors to IL-17e (IL-17Rh1fc) or IL-13 (IL-13Ralpha2Fc). Total IgE levels, in mice receiving the IL-17Rh1fc and IL-13Ralpha2Fc therapy, were lower …