Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or ...Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system. Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration.展开更多
Genetic diseases seriously threaten human health and have always been one of the refractory conditions facing humanity.Currently,gene therapy drugs such as siRNA,shRNA,antisense oligonucleotide,CRISPR/Cas9 system,plas...Genetic diseases seriously threaten human health and have always been one of the refractory conditions facing humanity.Currently,gene therapy drugs such as siRNA,shRNA,antisense oligonucleotide,CRISPR/Cas9 system,plasmid DNA and miRNA have shown great potential in biomedical applications.To avoid the degradation of gene therapy drugs in the body and effectively deliver them to target tissues,cells and organelles,the development of excellent drug delivery vehicles is of utmost importance.Viral vectors are the most widely used delivery vehicles for gene therapy in vivo and in vitro due to their high transfection efficiency and stable transgene expression.With the development of nanotechnology,novel nanocarriers are gradually replacing viral vectors,emerging superior performance.This review mainly illuminates the current widely used gene therapy drugs,summarizes the viral vectors and non-viral vectors that deliver gene therapy drugs,and sums up the application of gene therapy to treat genetic diseases.Additionally,the challenges and opportunities of the field are discussed from the perspective of developing an effective nano-delivery system.展开更多
Inflammatory bowel diseases(IBD)are a group of chronic inflammatory disorders most commonly affecting young adults.Currently available therapies can result in induction and maintenance of remission,but are not curativ...Inflammatory bowel diseases(IBD)are a group of chronic inflammatory disorders most commonly affecting young adults.Currently available therapies can result in induction and maintenance of remission,but are not curative and have sometimes important side effects.Advances in basic research in IBD have provided new therapeutic opportunities to target the inflammatory process involved.Gene and cell therapy approaches are suitable to prevent inflammation in the gastrointestinal tract and show therefore potential in the treatment of IBD.In this review,we present the current progress in the field of both gene and cell therapy and future prospects in the context of IBD.Regarding gene therapy,we focus on viral vectors and their applications in preclinical models.The focus for cell therapy is on regulatory T lymphocytes and mesenchymal stromal cells,their potential for the treatment of IBD and the progress made in both preclinical models and clinical trials.展开更多
The patient was found to have 4+urine sugar by physical examination 14 years ago and was treated with oral hypoglycemic drugs. Insulin was injected intramuscularly nine years ago. Two and a half years ago, it was foun...The patient was found to have 4+urine sugar by physical examination 14 years ago and was treated with oral hypoglycemic drugs. Insulin was injected intramuscularly nine years ago. Two and a half years ago, it was found that the color of the thumb, index and middle toe of the left foot became black. He went to a third-class hospital in Beijing and was diagnosed as “diabetes foot”. He was treated with “balloon dilation of lower limb blood vessels of diabetes foot”. Half a year ago, the third toe on the right side was broken and treated in the hospital again. “Popliteal artery stent implantation” was given for the diagnosis of “double kidney insufficiency, diabetes foot, left heart failure, combined heart valve disease”, “Hemofiltration therapy” and anti-inflammatory, amino acid supplementation, kidney function protection, anticoagulation, anemia correction and other treatments. Later, he went to our hospital and was diagnosed by the TCM diagnosis: category of consumptive disease, toe or finger gangrene (syndrome/pattern of qi and yin deficiency). Western medicine diagnosed: stage V of diabetes nephropathy, type II diabetes foot gangrene, combined with heart valve disease, hypoalbuminemia, double kidney cyst, moderate anemia, pleural effusion, hyperkalemia, pulmonary infection, and total heart failure. The patient was treated by the Qi-acupuncture therapy of TCM in combination with Chinese and Western medicine Medical treatment made the patient significantly better and discharged.展开更多
GM2 gangliosidoses are a group of autosomal-recessive lysosomal storage disorde rs.These diseases result from a deficiency of lysosomal enzymeβ-hexosaminidase A(HexA),which is responsible for GM2 ganglioside degradat...GM2 gangliosidoses are a group of autosomal-recessive lysosomal storage disorde rs.These diseases result from a deficiency of lysosomal enzymeβ-hexosaminidase A(HexA),which is responsible for GM2 ganglioside degradation.HexA deficiency causes the accumulation of GM2-gangliosides mainly in the nervous system cells,leading to severe progressive neurodegeneration and neuroinflammation.To date,there is no treatment for these diseases.Cell-mediated gene therapy is considered a promising treatment for GM2 gangliosidoses.This study aimed to evaluate the ability of genetically modified mesenchymal stem cells(MSCs-HEXA-HEXB)to restore HexA deficiency in Tay-Sachs disease patient cells,as well as to analyze the functionality and biodistribution of MSCs in vivo.The effectiveness of HexA deficiency cross-correction was shown in mutant MSCs upon intera ction with MSCs-HEXA-HEXB.The results also showed that the MSCs-HEXA-HEXB express the functionally active HexA enzyme,detectable in vivo,and intravenous injection of the cells does not cause an immune response in animals.These data suggest that genetically modified mesenchymal stem cells have the potentials to treat GM2 gangliosidoses.展开更多
文摘Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system. Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration.
基金supported by the National Natural Science Foundation of China(No.51472115)Double Firstclass Innovation Team of China Pharmaceutical University(CPU2018GY40).
文摘Genetic diseases seriously threaten human health and have always been one of the refractory conditions facing humanity.Currently,gene therapy drugs such as siRNA,shRNA,antisense oligonucleotide,CRISPR/Cas9 system,plasmid DNA and miRNA have shown great potential in biomedical applications.To avoid the degradation of gene therapy drugs in the body and effectively deliver them to target tissues,cells and organelles,the development of excellent drug delivery vehicles is of utmost importance.Viral vectors are the most widely used delivery vehicles for gene therapy in vivo and in vitro due to their high transfection efficiency and stable transgene expression.With the development of nanotechnology,novel nanocarriers are gradually replacing viral vectors,emerging superior performance.This review mainly illuminates the current widely used gene therapy drugs,summarizes the viral vectors and non-viral vectors that deliver gene therapy drugs,and sums up the application of gene therapy to treat genetic diseases.Additionally,the challenges and opportunities of the field are discussed from the perspective of developing an effective nano-delivery system.
基金Supported by A grant from the Broad Medical Research Program of The Broad Foundation,Proposal No.IBD-029 5R(to van der Marel S and Hommes DW)
文摘Inflammatory bowel diseases(IBD)are a group of chronic inflammatory disorders most commonly affecting young adults.Currently available therapies can result in induction and maintenance of remission,but are not curative and have sometimes important side effects.Advances in basic research in IBD have provided new therapeutic opportunities to target the inflammatory process involved.Gene and cell therapy approaches are suitable to prevent inflammation in the gastrointestinal tract and show therefore potential in the treatment of IBD.In this review,we present the current progress in the field of both gene and cell therapy and future prospects in the context of IBD.Regarding gene therapy,we focus on viral vectors and their applications in preclinical models.The focus for cell therapy is on regulatory T lymphocytes and mesenchymal stromal cells,their potential for the treatment of IBD and the progress made in both preclinical models and clinical trials.
文摘The patient was found to have 4+urine sugar by physical examination 14 years ago and was treated with oral hypoglycemic drugs. Insulin was injected intramuscularly nine years ago. Two and a half years ago, it was found that the color of the thumb, index and middle toe of the left foot became black. He went to a third-class hospital in Beijing and was diagnosed as “diabetes foot”. He was treated with “balloon dilation of lower limb blood vessels of diabetes foot”. Half a year ago, the third toe on the right side was broken and treated in the hospital again. “Popliteal artery stent implantation” was given for the diagnosis of “double kidney insufficiency, diabetes foot, left heart failure, combined heart valve disease”, “Hemofiltration therapy” and anti-inflammatory, amino acid supplementation, kidney function protection, anticoagulation, anemia correction and other treatments. Later, he went to our hospital and was diagnosed by the TCM diagnosis: category of consumptive disease, toe or finger gangrene (syndrome/pattern of qi and yin deficiency). Western medicine diagnosed: stage V of diabetes nephropathy, type II diabetes foot gangrene, combined with heart valve disease, hypoalbuminemia, double kidney cyst, moderate anemia, pleural effusion, hyperkalemia, pulmonary infection, and total heart failure. The patient was treated by the Qi-acupuncture therapy of TCM in combination with Chinese and Western medicine Medical treatment made the patient significantly better and discharged.
基金supported by the subsidy allocated to Kazan Federal University for the state assignment#0671-2020-0058 in the sphere of scientific activities(to AAR)the Kazan Federal University Strategic Academic Leadership Program(PRIORITY-2030)。
文摘GM2 gangliosidoses are a group of autosomal-recessive lysosomal storage disorde rs.These diseases result from a deficiency of lysosomal enzymeβ-hexosaminidase A(HexA),which is responsible for GM2 ganglioside degradation.HexA deficiency causes the accumulation of GM2-gangliosides mainly in the nervous system cells,leading to severe progressive neurodegeneration and neuroinflammation.To date,there is no treatment for these diseases.Cell-mediated gene therapy is considered a promising treatment for GM2 gangliosidoses.This study aimed to evaluate the ability of genetically modified mesenchymal stem cells(MSCs-HEXA-HEXB)to restore HexA deficiency in Tay-Sachs disease patient cells,as well as to analyze the functionality and biodistribution of MSCs in vivo.The effectiveness of HexA deficiency cross-correction was shown in mutant MSCs upon intera ction with MSCs-HEXA-HEXB.The results also showed that the MSCs-HEXA-HEXB express the functionally active HexA enzyme,detectable in vivo,and intravenous injection of the cells does not cause an immune response in animals.These data suggest that genetically modified mesenchymal stem cells have the potentials to treat GM2 gangliosidoses.
