• Archives of Pharmacal Research
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• v.24 no.1
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• pp.1-15
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• 2001

Gene therapy has emerged as a new concept of therapeutic strategies to treat diseases which do not respond to the conventional therapies. The principle of gene therapy is to Introduce genetic materials into patient cells to produce therapeutic proteins in these cells. Gene therapy is now at the stage where a number of clinical trials have been carried out to patients with gene-deficiency disease or cancer. Genetic materials for gene therapy are generally composed of gene expression system and gene delivery system. For the clinical application of gene therapy in a way which conventional drugs are used, researches have been focused on the design of gene delivery system which can offer high transfection efficiency with minimal toxicity. Currently, viral delivery systems generally provide higher transfection efficiency compared with non-viral delivery systems while non-viral delivery systems are less toxic, less immunogenic and manufacturable in large scale compared with viral systems. Recently, novel strategies towards the design of new non-viral delivery system, combination of viral and non-viral delivery systems and targeted delivery system have been extensively studied. The continued effort in this area will lead us to develop gene medicine as "gene as a drug" in the near future.

• Macromolecular Research
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• v.11 no.1
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• pp.19-24
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• 2003

Polymeric gene delivery system attracts profound attention as it shows less toxicity, versatility, and reasonable gene expression efficiency. Terplex system, a synthetic biopolymeric gene delivery system consisting of stearyl poly-L-lysine (stearyl-PLL) and low density lipoprotein (LDL) was evaluated for its body distribution of gene expression of exogenously administered pDNA after tail-vein injection in mice. Kidney and spleen are two major organs with highest gene expression, whereas liver and heart showed marginal gene expression among the organs examined. Hemolytic effect of the terplex system was evaluated using human red blood cells, where terplex system did not cause significant hemolysis at the concentrations above the experimental ranges, although unmodified PLL or stearyl-PLL without LDL did. Serum stability of terplex system against enzymatic degradation was also significantly enhanced, presumably due to the steric stabilization from the polymers. Based on these findings and along with its high in vitro transfection efficiency, terplex system could serve as a safe and efficient polymeric gene delivery system with many applications for the in vivo gene therapy.

• Proceedings of the Microbiological Society of Korea Conference
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• 2002.10a
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• pp.109-115
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• 2002

Gene therapy is to treat and cure diseases by an introduction of therapeutic genes in defective cells or tissues of human body. Gene delivery system, gene expression system, and therapeutic gene are three core elements for gene therapy. The efficient delivery of therapeutic genes and appropriate gene expression are the crucial issues for therapeutic outcome of gene delivery. Because it can be used in common for the treatment and cure of various diseases, gene delivery system is the most important core element for a successful gene therapy. Viruses are naturally evolved to transfer their genomes into host cells efficiently. This ability has made vectorologists exploit viruses as attractive vehicles for the delivery of therapeutic genes. Viral vectors based on adenovirus (Ad) and adeno-associated virus (AAV) have been often used for gene delivery in laboratory. Ad and AAV vectors derived from human DNA viruses differ greatly in their life cycle, expression level and duration of transgenes, immunogenicity, and vector preparation. Both vectors can be used as effective tools for gene therapy and more recently in functional genomics. Here, the characteristics of Ad and AAV vectors are discussed.

• Macromolecular Research
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• v.15 no.2
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• pp.100-108
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• 2007

Gene therapy has become a promising strategy for the treatment of genetically based diseases, such as cancer, which are currently considered incurable. A major obstacle in the field of cancer gene therapy is the development of a safe and efficient delivery system for therapeutic gene transfer. Non-viral vectors have attracted great interest, as they are simple to prepare, stable, easy to modify and relatively safe compared to viral vectors. In this review, an insight into the strategies developed for polyethylenimine (PEI)-based non-viral vectors has been provide, including improvement of the polyplex properties by incorporating hydrophilic spacer, poly(ethylene glycol) (PEG). Moreover, this review will summarize the strategies for the tumor targeting. Specifically, a targeted polymeric gene delivery system, PEI-g-PEG-RGD, will be introduced as an efficient gene delivery vector for tumor therapy, including its functional analysis both in vitro and in vivo.

• Journal of Pharmaceutical Investigation
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• v.30 no.1
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• pp.1-12
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• 2000

Gene therapy is a method for the treatment of diseases with introducing the gene-engineered materials into a patient with gene-deficiency disease (e.g. cystic fibrosis) or cancer to produce a therapeutic protein in a patient's cells. Successful gene therapy requires establishing both gene expression systems and delivery systems. Viral and non-viral vectors have been used for gene delivery. Viral vectors have a high transfection efficiency, but are limited in relations to issues of safety, toxicity and immunogenecity. Non-viral vectors are easy to prepare and relatively safe. However, non-viral vectors have a low transfection efficiency. Cationic liposomes are the most available among non-viral vectors. Cationic liposomes have been used to transfect cells both in vitro and in vivo experiments. Besides, several formulations containing cationic lipid are being used in clinical trials in cases of cystic fibrosis or cancer. A crucial subject to the further development of gene delivery vectors will be a long-term gene expression with following characteristics; protecting and deliverying DNA efficiently, non-toxic and non-immunogenic, and easy to produce in large scale.

• KSBB Journal
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• v.31 no.4
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• pp.300-311
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• 2016

Recently gene delivery has been designed newly using bioactive biomaterial and applied in the various field by many researchers. In this study, we proposed a new gene delivery system which has the capability of targeting effect in the specific tissue and remarkably enhanced transfection efficiency. We investigated $^1H-NMR$ spectroscopy, particle size analyzer and gel retardation to confirm the correct preparation of gene delivery. Also, we identified the hemo-compatibility of gene delivery by hemolysis assay, non-cytotoxicity by MTT test and transfection efficiency. The uptake mechanism of the gene carrier was confirmed using inhibitor agent such as sodium azide, indomethacin, quercetin, colchicine, and chloropromazine. As a results, it was identified that gene carrier prepared by in this study entered in the cell by the microtubule-dependent, energy-dependent and clathrin-mediated endocytosis pathway.

• Molecules and Cells
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• v.25 no.4
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• pp.462-466
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• 2008

Adenoviruses are the most commonly used gene-delivery vectors due to the efficiency of their in vivo gene transfer. Since 1993, about 300 protocols using an adenoviral vector have been performed, although they have yet to be proven effective in clinical trials. The adenovirus-based vector has been continuously improved by modification of the adenoviral genome and capsid, and novel adenovirus-delivery systems, such as the carrier-cell delivery system, have been recently proposed. Adenovirus-based cancer gene therapy is fast becoming one component of a multi-modality treatment approach to advanced cancer, along with surgery, radiotherapy, and chemotherapy.

• KSBB Journal
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• v.19 no.5
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• pp.341-347
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• 2004

Several gene delivery therapies are being developed for treatment of serum protein deficiency. EPO is one of the most promising therapeutic agent for this treatment which is currently being investigated in depth. This study has the ultimate purpose of improving the gene delivery system for an increase of red blood cell production. A plasmid DNA was constructed smaller than other plasmids for an increase in penetration into animal cells, and two genes were cloned into each vector as a co-delivery system to express erythropoietin, and interluekin-3 or thrombopoietin, which can act on erythroid cell, thus activating hematopoiesis synergically. This co-delivery system has an advantage of decreasing the labour required for industrial production of DNA vaccine. A new plasmid vector, pVAC, in size 2.9 kb, was constructed with the essential parts from PUC 19 and pSectagB, which is much smaller than other plasmid vector and is the size of 2.9 kb. Co-delivery system was constituted by cloning human erythropoietin with each of human interluekin-3 gene or human thrombopoietin gene into both pVAC and pSectagB. As a result, the transfection efficiency of pVAC was higer than that of pSectagB in vitro, and hematocrit level of the mice injected with pVAC is higher than that of other mice. And co-delivery system, made of several plasmid DNAs, was expressed in vitro.

• Journal of Pharmaceutical Investigation
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• v.32 no.3
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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.

• Archives of Pharmacal Research
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• v.25 no.3
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• pp.229-239
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• 2002

Recent progress in understanding the molecular basis of cancer brought out new materials such as oligonucleotides, genes, peptides and proteins as a source of new anticancer agents. Due to their macromolecular properties, however, new strategies of delivery for them are required to achieve their full therapeutic efficacy in clinical setting. Development of improved dosage forms of currently marketed anticancer drugs can also enhance their therapeutic values. Currently developed delivery systems for anticancer agents include colloidal systems (liposomes, emulsions, nanoparticles and micelles), polymer implants and polymer conjugates. These delivery systems have been able to provide enhanced therapeutic activity and reduced toxicity of anticancer agents mainly by altering their pharmacokinetics and biodistribution. Furthermore, the identification of cell-specific receptor/antigens on cancer cells have brought the development of ligand- or antibody-bearing delivery systems which can be targeted to cancer cells by specific binding to receptors or antigens. They have exhibited specific and selective delivery of anticancer agents to cancer. As a consequence of extensive research, clinical development of anticancer agents utilizing various delivery systems is undergoing worldwide. New technologies and multidisciplinary expertise to develop advanced drug delivery systems, applicable to a wide range of anticancer agents, may eventually lead to an effective cancer therapy in the future.