The Experts below are selected from a list of 53823 Experts worldwide ranked by ideXlab platform
Dong Zhou - One of the best experts on this subject based on the ideXlab platform.
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The potential Neurological Effect of the COVID-19 vaccines: A review.
Acta neurologica Scandinavica, 2021Co-Authors: Weixi Xiong, Qi Zhang, Hesheng Zhang, Ling Zou, Josemir W Sander, Dong ZhouAbstract:The coronavirus disease 2019 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic with people infected in almost all countries. The most efficient solution to end this pandemic is a safe and efficient vaccine. Classic platforms are used to develop vaccines including live-attenuated vaccine, inactivated vaccine, protein subunit vaccine, and viral vector. Nucleic acid vaccine uses next-generation platforms for their development. Vaccines are now rushing to the market. Eleven candidates are in advance development. These comprise inactivated vaccines, viral vector vaccine, nucleic acid vaccine, and the protein subunit vaccine platform, which are now quite advanced in trials in various geographic and ethnic populations. The reported severe adverse Effects raised the worries about their safety. It becomes critical to know whether these vaccines will cause neurologic disorders like previously recognized vaccine-related demyelinating diseases, fever-induced seizure, and other possible deficits. We reviewed the most promising COVID-2 vaccines with a particular interest in mechanism(s) and adverse Effect(s). We exemplify potential Neurological problems these vaccines could cause by looking at previous studies. The current evidence indicated a minor risk of the acute Neurological disorders after the application. The observation of the long-time Effect is still needed.
Michael C Holmes - One of the best experts on this subject based on the ideXlab platform.
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484 in vivo zinc finger nuclease mediated iduronate 2 sulfatase ids target gene insertion and correction of metabolic disease in a mouse model of mucopolysaccharidosis type ii mps ii
Molecular Therapy, 2016Co-Authors: Kanut Laoharawee, Russell Dekelver, Kelly M Podetzpetersen, Susan Tom, Robert Radeke, Michelle Rohde, Amy Manningbog, Scott Sproul, Kathleen Meyer, Michael C HolmesAbstract:Hunter syndrome (Mucopolysaccharidosis Type II, MPS II) is a rare X-linked lysosomal disorder caused by lack of functional iduronate-2 sulfatase (IDS) enzyme and subsequent accumulation of glycosaminoglycans (GAG) in affected individuals. Manifestations include skeleton dysplasia, splenohepatomegaly, cardiopulmonary obstruction, and shortened life expectancy. In severe cases there is also neurologic impairment. Enzyme replacement therapy (ERT) is currently the only FDA-approved treatment to manage disease progression; however, ERT does not affect Neurological aspects of the disease and requires that patients receive long and costly infusions of replacement factor on a frequent basis. We have developed a zinc-finger nuclease (ZFN) approach to insert the human IDS (hIDS) coding sequence into the albumin locus using AAV2/8 vectors. In this study IDS-deficient MPS II mice (n= 8-13 per group, age 7-8 weeks) were treated by intravenous infusion of a mixture of ZFN-encoding AAV vectors along with an AAV vector encoding the hIDS partial cDNA flanked by albumin sequence homology arms at three different vector doses. Wild-type littermates, untreated MPS II mice, and MPS II animals infused only with the hIDS donor vector (without ZFN-encoding vectors) were included as controls. Successful insertion of the hIDS coding sequence will result in hIDS expression regulated by the endogenous albumin promoter. Plasma and tissue IDS activities as well as urine and tissue GAG contents were monitored throughout the study to evaluate the Effectiveness of the treatment. Sufficient animals were maintained for neurobehavioral testing at four-months post-injection to determine whether the treatment is Neurologically beneficial. We found that IDS activities in the plasma of the treated groups were 10- to 100-fold higher than wild-type and stably expressed through the entire study duration in a dose-dependent fashion, while only very low levels of IDS activity were found in the animals infused with hIDS donor vector alone. At 4 weeks post-treatment IDS activities in peripheral tissues ranged from 1% to 200% wild-type in a dose-dependent fashion, while in the hIDS donor-only group enzyme activity was not detected in any tissue except liver (10% that of wild-type). We observed up to 2% of the wild-type IDS activity in the brains of animals administered the complete set of AAV vectors, while no IDS activity was observed in the brains of animals infused with the IDS donor vector alone. Urine GAGs were reduced in all of the ZFN + Donor treatment groups regardless of the vector dose. Tissue GAGs in the treatment groups were also decreased, but GAG content in the brain was not different from untreated MPS II litter mates at the initial analysis conducted four weeks post-treatment. No tissue GAG reduction was observed in animals infused with hIDS donor vector alone. Before conclusion of this study, animals from all six groups will be tested in the Barnes Maze as neurobehavioral assessment to determine the Neurological Effect of targeted hIDS expression in the liver. These results together with hIDS expression and GAG level data from final necropsy tissues will be presented. These results demonstrate that ZFN can be Effectively used to mediate in vivo insertion of the hIDS coding sequence into the albumin locus with resultant stable and high-level hIDS enzyme expression and metabolic correction in MPS II.
Weixi Xiong - One of the best experts on this subject based on the ideXlab platform.
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The potential Neurological Effect of the COVID-19 vaccines: A review.
Acta neurologica Scandinavica, 2021Co-Authors: Weixi Xiong, Qi Zhang, Hesheng Zhang, Ling Zou, Josemir W Sander, Dong ZhouAbstract:The coronavirus disease 2019 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic with people infected in almost all countries. The most efficient solution to end this pandemic is a safe and efficient vaccine. Classic platforms are used to develop vaccines including live-attenuated vaccine, inactivated vaccine, protein subunit vaccine, and viral vector. Nucleic acid vaccine uses next-generation platforms for their development. Vaccines are now rushing to the market. Eleven candidates are in advance development. These comprise inactivated vaccines, viral vector vaccine, nucleic acid vaccine, and the protein subunit vaccine platform, which are now quite advanced in trials in various geographic and ethnic populations. The reported severe adverse Effects raised the worries about their safety. It becomes critical to know whether these vaccines will cause neurologic disorders like previously recognized vaccine-related demyelinating diseases, fever-induced seizure, and other possible deficits. We reviewed the most promising COVID-2 vaccines with a particular interest in mechanism(s) and adverse Effect(s). We exemplify potential Neurological problems these vaccines could cause by looking at previous studies. The current evidence indicated a minor risk of the acute Neurological disorders after the application. The observation of the long-time Effect is still needed.
Kanut Laoharawee - One of the best experts on this subject based on the ideXlab platform.
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484 in vivo zinc finger nuclease mediated iduronate 2 sulfatase ids target gene insertion and correction of metabolic disease in a mouse model of mucopolysaccharidosis type ii mps ii
Molecular Therapy, 2016Co-Authors: Kanut Laoharawee, Russell Dekelver, Kelly M Podetzpetersen, Susan Tom, Robert Radeke, Michelle Rohde, Amy Manningbog, Scott Sproul, Kathleen Meyer, Michael C HolmesAbstract:Hunter syndrome (Mucopolysaccharidosis Type II, MPS II) is a rare X-linked lysosomal disorder caused by lack of functional iduronate-2 sulfatase (IDS) enzyme and subsequent accumulation of glycosaminoglycans (GAG) in affected individuals. Manifestations include skeleton dysplasia, splenohepatomegaly, cardiopulmonary obstruction, and shortened life expectancy. In severe cases there is also neurologic impairment. Enzyme replacement therapy (ERT) is currently the only FDA-approved treatment to manage disease progression; however, ERT does not affect Neurological aspects of the disease and requires that patients receive long and costly infusions of replacement factor on a frequent basis. We have developed a zinc-finger nuclease (ZFN) approach to insert the human IDS (hIDS) coding sequence into the albumin locus using AAV2/8 vectors. In this study IDS-deficient MPS II mice (n= 8-13 per group, age 7-8 weeks) were treated by intravenous infusion of a mixture of ZFN-encoding AAV vectors along with an AAV vector encoding the hIDS partial cDNA flanked by albumin sequence homology arms at three different vector doses. Wild-type littermates, untreated MPS II mice, and MPS II animals infused only with the hIDS donor vector (without ZFN-encoding vectors) were included as controls. Successful insertion of the hIDS coding sequence will result in hIDS expression regulated by the endogenous albumin promoter. Plasma and tissue IDS activities as well as urine and tissue GAG contents were monitored throughout the study to evaluate the Effectiveness of the treatment. Sufficient animals were maintained for neurobehavioral testing at four-months post-injection to determine whether the treatment is Neurologically beneficial. We found that IDS activities in the plasma of the treated groups were 10- to 100-fold higher than wild-type and stably expressed through the entire study duration in a dose-dependent fashion, while only very low levels of IDS activity were found in the animals infused with hIDS donor vector alone. At 4 weeks post-treatment IDS activities in peripheral tissues ranged from 1% to 200% wild-type in a dose-dependent fashion, while in the hIDS donor-only group enzyme activity was not detected in any tissue except liver (10% that of wild-type). We observed up to 2% of the wild-type IDS activity in the brains of animals administered the complete set of AAV vectors, while no IDS activity was observed in the brains of animals infused with the IDS donor vector alone. Urine GAGs were reduced in all of the ZFN + Donor treatment groups regardless of the vector dose. Tissue GAGs in the treatment groups were also decreased, but GAG content in the brain was not different from untreated MPS II litter mates at the initial analysis conducted four weeks post-treatment. No tissue GAG reduction was observed in animals infused with hIDS donor vector alone. Before conclusion of this study, animals from all six groups will be tested in the Barnes Maze as neurobehavioral assessment to determine the Neurological Effect of targeted hIDS expression in the liver. These results together with hIDS expression and GAG level data from final necropsy tissues will be presented. These results demonstrate that ZFN can be Effectively used to mediate in vivo insertion of the hIDS coding sequence into the albumin locus with resultant stable and high-level hIDS enzyme expression and metabolic correction in MPS II.
Ling Zou - One of the best experts on this subject based on the ideXlab platform.
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The potential Neurological Effect of the COVID-19 vaccines: A review.
Acta neurologica Scandinavica, 2021Co-Authors: Weixi Xiong, Qi Zhang, Hesheng Zhang, Ling Zou, Josemir W Sander, Dong ZhouAbstract:The coronavirus disease 2019 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic with people infected in almost all countries. The most efficient solution to end this pandemic is a safe and efficient vaccine. Classic platforms are used to develop vaccines including live-attenuated vaccine, inactivated vaccine, protein subunit vaccine, and viral vector. Nucleic acid vaccine uses next-generation platforms for their development. Vaccines are now rushing to the market. Eleven candidates are in advance development. These comprise inactivated vaccines, viral vector vaccine, nucleic acid vaccine, and the protein subunit vaccine platform, which are now quite advanced in trials in various geographic and ethnic populations. The reported severe adverse Effects raised the worries about their safety. It becomes critical to know whether these vaccines will cause neurologic disorders like previously recognized vaccine-related demyelinating diseases, fever-induced seizure, and other possible deficits. We reviewed the most promising COVID-2 vaccines with a particular interest in mechanism(s) and adverse Effect(s). We exemplify potential Neurological problems these vaccines could cause by looking at previous studies. The current evidence indicated a minor risk of the acute Neurological disorders after the application. The observation of the long-time Effect is still needed.