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Your search keyword '"Cheng, Seng"' showing total 24 results
Start Over Author "Cheng, Seng" Journal human gene therapy
24 results on '"Cheng, Seng"'

1. Translational Fidelity of Intrathecal Delivery of Self-Complementary AAV9–Survival Motor Neuron 1 for Spinal Muscular Atrophy

Author

Passini, Marco A., primary, Bu, Jie, additional, Richards, Amy M., additional, Treleaven, Christopher M., additional, Sullivan, Jennifer A., additional, O'Riordan, Catherine R., additional, Scaria, Abraham, additional, Kells, Adrian P., additional, Samaranch, Lluis, additional, San Sebastian, Waldy, additional, Federici, Thais, additional, Fiandaca, Massimo S., additional, Boulis, Nicholas M., additional, Bankiewicz, Krystof S., additional, Shihabuddin, Lamya S., additional, and Cheng, Seng H., additional

Published
2014
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3. Ability of Adeno-Associated Virus Serotype 8-Mediated Hepatic Expression of Acid α-Glucosidase to Correct the Biochemical and Motor Function Deficits of Presymptomatic and Symptomatic Pompe Mice

Author

Ziegler, Robin J., primary, Bercury, Scott D., additional, Fidler, Jonathan, additional, Zhao, Michael A., additional, Foley, Joseph, additional, Taksir, Tatyana V., additional, Ryan, Susan, additional, Hodges, Bradley L., additional, Scheule, Ronald K., additional, Shihabuddin, Lamya S., additional, and Cheng, Seng H., additional

Published
2008
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7. Enhancement of Fas Ligand-Induced Inhibition of Neointimal Formation in Rabbit Femoral and Iliac Arteries by Coexpression of p35

Author

Luo, Zhengyu, primary, Garron, Tracy, additional, Palasis, Maria, additional, Lu, Hsienwie, additional, Belanger, Adam J., additional, Scaria, Abraham, additional, Vincent, Karen A., additional, Date, Taro, additional, Akita, Geoffrey Y., additional, Cheng, Seng H., additional, Barry, James, additional, Gregory, Richard J., additional, and Jiang, Canwen, additional

Published
2001
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17. Basis of Pulmonary Toxicity Associated with Cationic Lipid-Mediated Gene Transfer to the Mammalian Lung

Author

Scheule, Ronald K., primary, George, Judith A. St., additional, Bagley, Rebecca G., additional, Marshall, John, additional, Kaplan, Johanne M., additional, Akita, Geoffrey Y., additional, Wang, Kathryn X., additional, Lee, Edward R., additional, Harris, David J., additional, Jiang, Canwen, additional, Yew, Nelson S., additional, Smith, Alan E., additional, and Cheng, Seng H., additional

Published
1997
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19. Detailed Analysis of Structures and Formulations of Cationic Lipids for Efficient Gene Transfer to the Lung

Author

Lee, Edward R., primary, Marshall, John, additional, Siegel, Craig S., additional, Jiang, Canwen, additional, Yew, Nelson S., additional, Nichols, Margaret R., additional, Nietupski, Jennifer B., additional, Ziegler, Robin J., additional, Lane, Mathieu B., additional, Wang, Kathryn X., additional, Wan, Nick C., additional, Scheule, Ronald K., additional, Harris, David J., additional, Smith, Alan E., additional, and Cheng, Seng H., additional

Published
1996
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21. Efficiency of Cationic Lipid-Mediated Transfection of Polarized and Differentiated Airway Epithelial Cells In Vitroand In Vivo

Author

Jiang, Canwen, O'Connor, Sean P., Fang, Shaona L., Wang, Kathryn X., Marshall, John, Williams, Jennifer L., Wilburn, Brian, Echelard, Yann, and Cheng, Seng H.

Abstract

ABSTRACTSystematic analysis of a large number of different cationic lipids has led to the identification of novel structures (GL-67) and formulations of cationic lipid:plasmid DNA (pDNA) complexes that facilitate high levels of gene expression in lungs of mice. However, despite significant improvement in gene transfer activity, we show here that the efficiency of GL-67-mediated gene transduction of intact airway epithelia is still relatively low. Administration of GL-67:pCF1-CFTR (encoding the cystic fibrosis transmembrane conductance regulator) complexes into the nasal epithelium of cystic fibrosis (CF) transgenic mice resulted only in marginal correction of the ion transport defects. Measurements of nasal potential differences (PD) showed no correction of the sodium (Na) transport defect, and only partial restitution of the chloride (Cl) transport defect was achieved in a small proportion of the animals after perfusion of the nasal epithelium with the complexes. Furthermore, in contrast to results obtained following instillation of GL-67:pDNA complexes into the lungs of mice, perfusion of GL-67:pDNA into the nasal epithelium resulted only in a moderate enhancement of gene transduction activity relative to that attained with naked pDNA alone. To determine the basis for this low efficiency of transfection, a series of studies was conducted to identify some of the barriers governing cationic lipid-mediated gene transfer to the airway epithelium. We show here that the transfection activity of GL-67 was affected by the polarization, differentiation, and proliferative state of the cells. Diminished transfection activity was observed with nonmitotic, highly polarized and differentiated airway epithelial cells. This observed reduction in gene expression with nonmitotic cells was determined to be due in part to inefficient nuclear translocation of the pDNA from the cytoplasm. Together these data indicate that much improvement in the ability of cationic lipids to transfect polarized and differentiated airway epithelial cells is a necessary prerequisite for effective cationic lipid-mediated gene therapy of airway diseases such as CF.

Published
1998
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22. Aerosolization of Cationic Lipid:pDNA ComplexesIn VitroOptimization of Nebulizer Parameters for Human Clinical Studies

Author

Eastman, Simon J., Tousignant, Jennifer D., Lukason, Michael J., Chu, Qiuming, Cheng, Seng H., and Scheule, Ronald K.

Abstract

ABSTRACTPreviously, we have described the optimization of the aerosol delivery of a nonviral gene therapy vector to the lungs of rodents (Eastman et al., 1997b). Although aerosolizing cationic lipid:pDNA complexes into a whole-body exposure chamber resulted in high levels of reporter gene expression in the lungs of BALB/c mice, the conditions employed were not optimal for the delivery of lipid:pDNA complexes to the lungs of human patients. That is, the consumption rate of the material in the nebulizer, and thus the delivery time, were very slow and the aerosol was delivered in a continuous flow. Here we describe in vitroexperiments used to develop a cationic lipid:pDNA aerosol with characteristics more suitable for delivery to the lungs of humans, as a necessary prerequisite for conducting a clinical study with human cystic fibrosis patients. Using cascade impactors and all-glass impingers, we have screened several commercially available nebulizers for their ability to deliver intact, respirable, active lipid:pDNA complexes in the shortest time possible, and have identified the Pari LC Jet Plus nebulizer as the optimal nebulizer that meets these criteria. Using this nebulizer in an intermittent mode to mimic breath actuation, consumption rates of approximately 0.6 ml/min of the cationic lipid:pDNA complexes (6 mMcationic lipid:8 mMpDNA) were obtained. The plasmid DNA remained intact and the complexes were shown to maintain activity throughout the nebulization run. Based on measurements of the nebulized dose and the mass median aerodynamic diameter, we calculate a delivered dose of ~ 22 mol (7.2 mg) of pDNA for each 8 ml of cationic lipid:pDNA complex aerosolized to the lungs of a human patient. This dose should be sufficient to test the clinical efficacy of cationic lipid-mediated gene delivery for the treatment of cystic fibrosis.

Published
1998
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23. Optimization of Formulations and Conditions for the Aerosol Delivery of Functional Cationic Lipid:DNA Complexes

Author

Eastman, Simon J., Tousignant, Jennifer D., Lukason, Michael J., Murray, Heather, Siegel, Craig S., Constantino, Paul, Harris, David J., Cheng, Seng H., and Scheule, Ronald K.

Abstract

ABSTRACTWe have examined several variables inherent in aerosolizing cationic lipid:DNA complexes using a jet nebulizer and thereby have optimized the delivery of functional complexes. Maximal aerosol transfer efficiency of cationic lipid:pDNA complexes was quantitated and shown to require the presence of at least 25 mMNaCl as an excipient. This is possibly related to effects on the measured zeta potentials of the complex, which indicate that the complexes are more highly charged in solutions of physiological ionic strength than in solutions of low ionic strength. Inclusion of saline also resulted in retention of the starting lipid to plasmid DNA (pDNA) ratio following nebulization. These data were used to design in vitroaerosolization experiments with tissue culture cells that resulted in the identification of a cationic lipid:pDNA ratio of 0.75:1 (mol:mol) as being optimal for aerosolization. This formulation largely protected pDNA from shear degradation during nebulization and produced a respirable aerosol droplet size (13 m). It was tested further in a mouse model and shown to result in the dose-dependent transfection of mouse lungs, generating the equivalent of several picograms of reporter gene activity per mouse lung. The results of these experiments have provided a set of optimal conditions for nebulizing cationic lipid:pDNA complexes that can be used as a starting point for the further evaluation of aerosol delivery of these nonviral gene delivery vectors in vivo.

Published
1997
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24. Ability of adeno-associated virus serotype 8-mediated hepatic expression of acid alpha-glucosidase to correct the biochemical and motor function deficits of presymptomatic and symptomatic Pompe mice.

Author

Ziegler RJ, Bercury SD, Fidler J, Zhao MA, Foley J, Taksir TV, Ryan S, Hodges BL, Scheule RK, Shihabuddin LS, and Cheng SH

Subjects
Animals, Disease Models, Animal, Glycogen Storage Disease Type II complications, Humans, Liver Glycogen genetics, Liver Glycogen metabolism, Mice, Mice, Mutant Strains, Motor Activity, Muscle, Skeletal pathology, Muscle, Skeletal physiopathology, Muscular Diseases etiology, Muscular Diseases physiopathology, Muscular Diseases therapy, alpha-Glucosidases blood, Dependovirus, Genetic Vectors, Glycogen Storage Disease Type II physiopathology, Glycogen Storage Disease Type II therapy, Liver enzymology, alpha-Glucosidases genetics
Abstract

The availability of a murine model of Pompe disease has enabled an evaluation of the relative merits of various therapeutic paradigms, including gene therapy. We report here that administration of a recombinant adeno-associated virus serotype 8 (AAV8) vector (AAV8/DC190-GAA) encoding human acid alpha-glucosidase (GAA) into presymptomatic Pompe mice resulted in nearly complete correction of the lysosomal storage of glycogen in all the affected muscles. A relatively high dose of AAV8/DC190-GAA was necessary to attain a threshold level of GAA for inducing immunotolerance to the expressed enzyme and for correction of muscle function, coordination, and strength. Administration of AAV8/DC190-GAA into older Pompe mice with overt disease manifestations was also effective at correcting the lysosomal storage abnormality. However, these older mice exhibited only marginal improvements in motor function and no improvement in muscle strength. Examination of histologic sections showed evidence of skeletal muscle degeneration and fibrosis in aged Pompe mice whose symptoms were abated or rescued by early but not late treatment with AAV8/DC190-GAA. These results suggest that AAV8-mediated hepatic expression of GAA was effective at addressing the biochemical and functional deficits in Pompe mice. However, early therapeutic intervention is required to maintain significant muscle function and should be an important consideration in the management and treatment of Pompe disease.

Published
2008
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