OBJECTIVE: To investigate a Met-controlled allosteric module (AM) of neural generation as a potential therapeutic target for brain ischemia. METHODS: We selected Markov clustering algorithm (MCL) to mine functional modules in the related target networks. According to the topological similarity, one functional module was predicted in the modules of baicalin (BA), jasminoidin (JA), cholic acid (CA), compared with I/R model modules. This functional module included three genes: Inppl1, Met and Dapk3 (IMD). By gene ontology enrichment analysis, biological process related to this functional module was obtained. This functional module participated in generation of neurons. Western blotting was applied to present the compound-dependent regulation of IMD. Co-immunoprecipitation was used to reveal the relationship among the three members. We used IF to determine the number of newborn neurons between compound treatment group and ischemia/reperfusion group. The expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) were supposed to show the changing circumstances for neural generation under cerebral ischemia. RESULTS: Significant reduction in infarction volume and pathological changes were shown in the compound treatment groups compared with the I/R model group (P<0.05). Three nodes in one novel module of IMD were found to exert diverse compound-dependent ischemic-specific excitatory regulatory activities. An anti-ischemic excitatory allosteric module (AM CONCLUSIONS AM
Animals ; Brain Ischemia/drug therapy* ; Gene Ontology ; Gene Regulatory Networks ; Rodentia ; Vascular Endothelial Growth Factor A

The overall goal of our research projects is to develop effective immunotherapeutic regimens, particularly combining vaccine and gene therapy/ cell therapy strategies. For the development of clinically effective immunotherapy for brain cancers, the following issues are considered to be particularly important: 1) Induction of effective immune responses against tumors (afferent arm of the immune response), 2) Delivery of immune effector cells to the target tumor sites and maintaining the activity of the effector cells (efferent arm), 3) For specific and safe immunotherapy, specific brain tumor rejection antigens have to be identified, 4) Feasibility, safety and efficacy need to be tested in a series of clinical trials. The following presentation summarizes my research projects and demonstrates how each plan will fit in the whole schema of designing successful immunotherapeutic strategies for brain cancers. In this presentation, I would like to focus on our clinical and basic studies related to the vaccine strategies for patients with glioma, and modulation of tumor-microenvironment using bone-marrow derived stroma cells as vehicles for cytokine- gene delivery.
*Biological Therapy ; Brain Neoplasms/*therapy ; Cancer Vaccines/*therapeutic use ; Cytokines/*genetics ; *Gene Therapy ; Humans

The targeted delivery of genes and the transplantation of suitable cell types into the adult nervous system have received considerable interest over the last years. The development of improved vector systems for in vivo gene delivery and the discovery of neural stem cells in the adult nervous system have opened new venues for potential therapeutic intervention in progressive neurodegenerative disease and nervous system injury. Thus, strategies have evolved for the delivery of potentially neuroprotective molecules, such as neurotrophic factors, and the replacement of cells and tissue lost due to CNS injury and degeneration.
Alzheimer Disease/*therapy ; *Cell Transplantation ; *Gene Therapy ; Humans ; Spinal Cord Injuries/*therapy

Hemophilia A(HA) is an X-linked recessive bleeding disorder caused by mutations in coagulation factor VIII. Nowadays, exogenous coagulation factor replacement therapy is the main treatment. With the continuous development of gene therapy, new research directions have been provided for the treatment of hemophilia A. CRISPR-Cas9 technology was applied to select suitable target sites, and mediate the targeted knock-in and efficient expression of exogenous B-domain-deleted FⅧ variant gene through corresponding vectors for the treatment of hemophilia A.CRISPR-Cas9 technology is an emerging gene editing tool with great efficiency, safety and effectiveness, and has been widely used in hemophilia gene therapy research. This paper reviews the vector selection, construction of therapeutic genes, gene editing technology and selection of expression target sites for hemophilia A gene therapy at this stage.
Humans ; Hemophilia A/therapy* ; CRISPR-Cas Systems ; Hemophilia B/therapy* ; Gene Editing ; Genetic Therapy ; Genetic Vectors

RNA interference (RNAi) is the sequence-specific gene silencing induced by double-stranded RNA (dsRNA). Being a highly specific and efficient knockdown technique, RNAi not only provides a powerful tool for functional genomics but also holds a promise for gene therapy. The key player in RNAi is small RNA (~22-nt) termed siRNA. Small RNAs are involved not only in RNAi but also in basic cellular processes, such as developmental control and heterochromatin formation. The interesting biology as well as the remarkable technical value has been drawing widespread attention to this exciting new field.
Animals ; Gene Therapy/*methods/trends ; *Genomics ; Human ; *RNA Interference

The rapid progress of molecular genetic methods over the past two decades has necessitated the development of methods to detect and quantify genetic activity within living bodies. Reporter genes provide a rapid and convenient tool to monitor gene expression by yielding a readily measurable phenotype upon expression when introduced into a biological system. Conventional reporter systems, however, are limited in their usefulness for in vivo experiments or human gene therapy because of its invasive nature which requires cell damage before assays can be performed. This offers an unique opportunity for nuclear imaging techniques to develope a novel method for imaging both the location and amount of gene expression noninvasively. Current developments to achieve this goal rely on utilizing either reporter enzymes that accumulate radiolabeled substrates or reporter receptors that bind specific radioligands. This overview includes a brief introduction to the background for such research, a summary of publis hed results, and an outlook for future directions.
Gene Expression* ; Genes, Reporter ; Genetic Therapy ; Humans ; Molecular Biology ; Phenotype

OBJECTIVE: The aim of this study is to find out the genes which are related to ovarian cancer cell growth using large circular antisense library. METHODS: Clones for antisense library were uni-directionally sub-cloned into pBS SK (-) vector. LC-antisense molecules were then purified from the culture supernatants of the bacterial competent cells superinfected with M13K07 helper bacteriophages. The LC-antisense library to 240 unigene clone was constructed and utilized in the identification of genes functionally involved in the growth of ovarian cancer cells. RESULTS: The 17 numbers out of the 240 numbers of the antisense library exerted a marked inhibitory effect on the growth of SK-OV 3. CONCLUSION: The putative functional categorization of each gene was then conducted via public databases. These candidates may be used as target genes for drug development or adjuvant of conventional chemotherapeutic drugs.
Bacteriophages ; Clone Cells ; Estrone ; Gene Targeting ; Genetic Therapy ; Ovarian Neoplasms

Recombinant adenovirus vector systems with strong promoters have been used to achieve high level production of recombinant protein. However, this overexpression system cause some problems such as disturbance of cell physiology and increment of cellular toxicity. Here, we showed a tetracycline-regulated adenovirus expression vector system. Our results showed that the expression level of transgene(p-53) was high and easily regulated by tetracycline. In addition, the maximal gene expresion level of the tetracycline-controlled gene expression system was higher than that of the wild type CMV promoter system. Therefore, tetracycline-regulated adenoviral vector system could be applicable for regulatory high-level expression of toxic gene. Also, this system will be useful for functional studies and gene therapy.
Adenoviridae* ; Cell Physiological Phenomena ; Gene Expression ; Genetic Therapy ; Tetracycline

Recent progress in the development of non-invasive imaging technologies continues to strengthen the role of molecular imaging biological research. These tools have been validated recently in variety of research models, and have been shown to provide continuous quantitative monitoring of the location (s), magnitude, and time-variation of gene expression. This article reviews the principles, characteristics, categories and the use of radionuclide reporter gene imaging technologies as they have been used in imaging cell trafficking, imaging gene therapy, imaging endogenous gene expression and imaging molecular interactions. The studies published to date demonstrate that reporter gene imaging technologies will help to accelerate pre-clinical model validation as well as allow for clinical monitoring of human diseases.
Gene Expression ; Genes, Reporter* ; Genetic Therapy ; Humans ; Molecular Imaging

In the 1960s, scientists first raised the idea of curing genetic diseases using gene therapy. This new conceptual strategy aimed to achieve a much longer therapeutic effect by introducing exogenous genetic materials into the patients. After more than five decades of ups and downs, gene therapy has been brought into a new era by those milestone breakthroughs in the 21st century. Here we reviewed and summarized the history and breakthroughs of gene therapy, including some critical clinical trials, approved drugs, and emerging gene editing techniques. We believe that with their unique advantages over traditional therapies, more gene therapies will become practical approaches to genetic diseases and benefit the entire human race.
CRISPR-Cas Systems ; Gene Editing ; Genetic Therapy ; Humans