• 대한핵의학회지
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• 제38권2호
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• pp.175-179
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• 2004

Molecular nuclear cardiac imaging has included Tc-99m Annexin imaging to visualize myocardial apoptosis, but is now usually associated with gene therapy and cell-based therapy. Cardiac gene therapy was not successful so far but cardiac reporter gene imaging was made possible using HSV-TK (herpes simplex virus thymidine kinase) and F-18 FHBG (fluoro-hydroxymethylbutyl guanine) or I-124 FIAU (fluoro-deoxyiodo-arabino-furanosyluracil). Gene delivery was performed by needic injection with or without catheter guidance. Tk expression did not last longer than 2 weeks in myocardium. Cell-based therapy of ischemic heart or failing heart looks promising, but biodistribution and differentiation of transplanted cells are not known. Reporter genes can be transfected to the stem/progenitor cells and cells containing these genes can be transplanted to the recipients using catheter-based purging or injection. Repeated imaging should be available and if promoter are varied to let express reporter transgenes, cellular (trans)differentiation can be studied. NIS (sodium iodide symporter) or D2R receptor genes are promising in this aspect.

• Journal of Pharmaceutical Investigation
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• 제32권3호
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• pp.153-159
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• 2002

Gene therapy is fundamentally a sophisticated drug delivery technology to cure a disease by the transfer of genetic material to modify living cells. In other words, the gene is used as a therapeutic drug much like a chemical compound is employed in chemotherapy. Currently almost 600 clinical trials are underway worldwide since the first clinical trials carried out in 1990 to treat adenosine deaminase deficiency using retroviral vectors. Despite the great progress still is there no gene therapy product being approved as a new drug. This is partly due to a lack of an ideal gene delivery system that is safe and can provide stable, optimal level production of the therapeutic proteins in the cell. This review covers the current status of several different biological and physico-chemical agents that are being developed as gene delivery vehicles. Although gene therapy promises great hopes toward the cure of a broad spectrum of genetic and acquired diseases, the success of gene therapy heavily asks for the development of vector systems for safe and efficient application in humans.

• Journal of mucopolysaccharidosis and rare diseases
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• 제5권1호
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• pp.22-28
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• 2021

Mucopolysaccharidosis type III (MPS III) or Sanfilippo disease is an orphan-inherited lysosomal storage disease. It is one of the most common MPS subtypes. The classical presentation is an infantile-onset neurodegenerative disease characterized by intellectual regression, behavioral and sleep disturbances, loss of ambulation, and early death. Unlike other MPS, no disease-modifying therapy has been approved. Here, we review the curative therapy developed for MPS III, from historically ineffective hematopoietic stem cell transplantation and substrate reduction therapy to the promising enzyme replacement therapy or adeno-associated/lentiviral vector-mediated gene therapy. Preclinical studies are presented with recent translational first-in-man trials. We also present experimental research with preclinical mRNA and gene-editing strategies. Lessons from animal studies and clinical trials have highlighted the importance of early therapy before extensive neuronal loss. Disease-modifying therapy for MPS III will likely mandate the development of new early diagnosis strategies.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 추계학술대회
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• pp.35-39
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• 1997

Recent development of human genetics and techniques of gene transfer and expression have opened the way for investigating novel approaches based on the genetic modification of cells to treat both inherited and acquired diseases. This approach is referred to as gene therapy. Over the past few years, gene therapy has moved from the laboratory to phase I clinical trials. Although the clinical performance of gene transfer experiments is still in an early phase of development, the NIH of Health Recombinant DNA Advisory Comittee (RAC) has approved more than 150 protocols that involve gene transfer or putative gene therapy procedures in clinical settings. Many sectors of society in United States have participated in the design and formulation of these clinical trials through local Institutional Review Boards, the National Institutes of Health (NIH) RAC, the Chemotherapy Evaluation Program of the National Cancer institute, and the FDA. Currently, clinical trials involving gene modification are under way at many medical centers throughout the United Slates. The goals of these trials are as follows. (1) The design should be directed to short-term achievable goals. (2) Each clinical trial is best considered as an intermediate step in a multistep process. (3) The design should identify evaluable proximate endpoints for toxicity and for efficacy, (4) The potential benefits and possible risks for patients participating in these trial should be defined.

• BMB Reports
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• 제57권1호
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• pp.2-11
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• 2024

Advancements in gene and cell therapy have resulted in novel therapeutics for diseases previously considered incurable or challenging to treat. Among the various contributing technologies, genome editing stands out as one of the most crucial for the progress in gene and cell therapy. The discovery of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and the subsequent evolution of genetic engineering technology have markedly expanded the field of target-specific gene editing. Originally studied in the immune systems of bacteria and archaea, the CRISPR system has demonstrated wide applicability to effective genome editing of various biological systems including human cells. The development of CRISPR-based base editing has enabled directional cytosine-to-thymine and adenine-to-guanine substitutions of select DNA bases at the target locus. Subsequent advances in prime editing further elevated the flexibility of the edit multiple consecutive bases to desired sequences. The recent CRISPR technologies also have been actively utilized for the development of in vivo and ex vivo gene and cell therapies. We anticipate that the medical applications of CRISPR will rapidly progress to provide unprecedented possibilities to develop novel therapeutics towards various diseases.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.4133-4136
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• 2015

Background: To analyze multi-source data including publications and patents, and try to draw the whole landscape of the research and development community in the field of gene therapy for breast cancer. Materials and Methods: Publications and patents were collected from the Web of science and databases of the five major patent offices of the world, respectively. Bibliometric methodologies and technology are used to investigate publications/patents, their contents and relationships. Results: A total of 2,043 items published and 947 patents from 1994 to 2013 including "gene therapy for breast cancer" were retrieved. The top five countries in global publication share were USA, China, Germany, Japan and England. On the other hand, USA, Australia, England, South Korea and Japan were the main producers of patents. The universities and enterprises of USA had the highest amount of publication and patents. Adenovirus- and retrovirus-based gene therapies and small interfering RNA (siRNA) interference therapies were the main topics both in publications and patents. Conclusions: The above results show that global research in the field of gene therapy for breast cancer is increasing and the main participants in this field are USA and Canada in North America, China, Japan and South Korea in Asia, and England, Germany, and Italy in Europe. Also, this article demonstrates the usefulness of bibliometrics to address key evaluation questions and define future areas of research.

• Journal of Microbiology and Biotechnology
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• 제30권9호
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• pp.1273-1281
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• 2020

Due to the broad host suitability of viral vectors and their high gene delivery capacity, many researchers are focusing on viral vector-mediated gene therapy. Among the retroviruses, foamy viruses have been considered potential gene therapy vectors because of their non-pathogenicity. To date, the prototype foamy virus is the only retrovirus that has a high-resolution structure of intasomes, nucleoprotein complexes formed by integrase, and viral DNA. The integration of viral DNA into the host chromosome is an essential step for viral vector development. This process is mediated by virally encoded integrase, which catalyzes unique chemical reactions. Additionally, recent studies on foamy virus integrase elucidated the catalytic functions of its three distinct domains and their effect on viral pathogenicity. This review focuses on recent advancements in biochemical, structural, and functional studies of foamy virus integrase for gene therapy vector research.

• Genomics & Informatics
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• 제16권4호
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• pp.20.1-20.20
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• 2018

Genetic hearing loss crosses almost all the categories of hearing loss which includes the following: conductive, sensory, and neural; syndromic and nonsyndromic; congenital, progressive, and adult onset; high-frequency, low-frequency, or mixed frequency; mild or profound; and recessive, dominant, or sex-linked. Genes play a role in almost half of all cases of hearing loss but effective treatment options are very limited. Genetic hearing loss is considered to be extremely genetically heterogeneous. The advancements in genomics have been instrumental to the identification of more than 6,000 causative variants in more than 150 genes causing hearing loss. Identification of genes for hearing impairment provides an increased insight into the normal development and function of cells in the auditory system. These defective genes will ultimately be important therapeutic targets. However, the auditory system is extremely complex which requires tremendous advances in gene therapy including gene vectors, routes of administration, and therapeutic approaches. This review summarizes and discusses recent advances in elucidating the genomics of genetic hearing loss and technologies aimed at developing a gene therapy that may become a treatment option for in the near future.

• Reproductive and Developmental Biology
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• 제28권4호
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• pp.247-252
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• 2004

Human embryonic stem (ES) cells are derived from the inner cell mass of the preimplantation embryo. Human ES cells have the capacity to differentiate into various types of cells in the body. Human ES cells are indefinite source of cells for cell therapy in various degenerative disorders including neuronal disorders. Directed differentiation of human ES cells is a prerequisite for their clinical application. The objective of this study is to develop the culture condition for the derivation of neural precursor cells from human ES cells. Neural precursor cells were derived from human ES cells in a stepwise culture condition. Neural precursor cells in the form of neural rosette structures developed into neurospheres when cultured in suspension. Suspension culture of neurospheres has been maintained over 4 months. Expressions of nestin, soxl, sox2, pax3 and pax6 transcripts were upregulated during differentiation into neural precursor cells by RT-PCR analysis. In contrast, expression of oct4 was dramatically downregulated in neural precursor cells. Immunocytochemical analyses of neural precursor cells demonstrated expression of nestin and SOX1. When induced to differentiate on an adhesive substrate, neuro-spheres were able to differentiate into three lineages of neural systems, including neurons, astrocytes and oligo-dendrocytes. Transcripts of sox1 and pax6 were downregulated during differentiation of neural precursor cells into neurons. In contrast, expression of map2ab was elevated in the differentiated cells, relative to those in neural precursor cells. Neurons derived from neural precursor cells expressed NCAM, Tuj1, MAP2ab, NeuN and NF200 in immunocytochemical analyses. Presence of astrocytes was confirmed by expression of GFAP immuno-cytochemically. Oligodendrocytes were also observed by positive immuno-reactivities against oligodendrocyte marker O1. Results of this study demonstrate that a stepwise culture condition is developed for the derivation of neural precursor cells from human ES cells.

• 대한약리학회:학술대회논문집
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• 대한약리학회 2006년도 The 6th Congress of the Federation of Asian and Oceanian Physiological Societies
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• pp.68-68
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• 2006