• Tuberculosis and Respiratory Diseases
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• 제44권6호
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• pp.1271-1284
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• 1997

연구배경 : 종양괴사인자(tumor necrosis factor ; TNF)는 다양한 생물학적 기능을 가지고 있는 바, 그 중 생체 외에서 증명된 뚜렷한 항암 효과로 말미암아 최근 항암 유전자요법의 중요한 대상으로 관심을 모으고 있다. 현재 유전자 이입의 기술적 문제로 생체 외에서 암세포에 유전자 이입을 시행한 후 이를 다시 환자의 생체내로 이식하는 방법이 연구의 주종을 이루고 있다. 그러나 저자들의 과거의 연구를 포함한 여러 연구에서 TNF가 이입된 암세포는 TNF에 대해 내성을 보이는 것으로 증명되었고 이에는 새로이 방어 단백질을 합성하는 것이 관여할 것이라는 시사가 있었다. 이 획득내성의 기전을 밝히는 것이 종양생물학의 이해를 넓히고 보다 효과적인 항암 유전자요법을 개발하기위한 매우 중요한 과제로 생각된다.

• 폴리머
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• 제38권1호
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• pp.43-48
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• 2014

본 논문은 저분자량의 폴리에틸렌이민을 폴리디아세틸렌 리포좀 표면에 연결하여 유전자를 세포 내로 전달할 수 있는 새로운 양이온성 고분자 리포좀 유전자 전달체 개발에 대한 결과이다. 폴리디아세틸렌 리포좀 제조 후에 자외선을 조사하여 고분자성 리포좀을 제조한 후, 유전자의 전달 효율을 높이기 위해 폴리에틸렌이민을 리포좀 표면에 커플링제를 이용하여 공유결합시켜서 PCDA-PEI 리포좀을 합성하였다. 제조한 고분자 리포좀을 이용하여 동물세포 내에서의 유전자 전달 및 발현 효율과 그에 따른 독성을 확인하는 연구를 수행하였다. 사용한 폴리에틸렌이민은 가지형이고 분자량은 2 kD인 것을 사용하였다. DNA와의 복합체 형성을 알아보기 위하여 전기영동 방법과 피코그린 형광 염색 시약을 사용하였으며 효율적으로 복합체를 형성하는 것을 확인하였다. 전달체의 효율과 독성을 확인하기 위하여 HEK 293 및 HeLa 세포를 사용하여 확인하였다. 실험 결과 PCDA-PEI 리포좀은 세포 내에서 비율이 높아질수록 유전자 전달 효율이 증가하는 경향을 보였고, 세포에 대한 독성도 상대적으로 낮음을 확인하였다. 이러한 결과는 PCDA-PEI 리포좀이 효율적인 유전자 혹은 약물 전달체로 사용될 수 있음을 보여주었다.

• Bulletin of the Korean Chemical Society
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• 제25권7호
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• pp.1025-1030
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• 2004

A hybrid linear polymer-dendrimer block copolymer, poly(ethylene glycol)-block-poly(L-lysine) dendrimer, was synthesized and introduced to form polyionic complexes with DNA. The copolymer formed core-shell type nanoparticles with plasmid DNA. From dynamic light scattering experiments, the mean diameter of the polyplexes was observed to be 154.4 nm. The complex showed much increased water solubility compared to poly(L-lysine). The plasmid DNA in polyplexes was efficiently protected from the enzymatic digestion of DNase I. The cytotoxicity and transfection efficiency for 293 cells was measured in comparison with poly(Llysine).

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.425.3-426
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• 2002

Cationic lipids have been used as one of the major components for making most promising non-viral gene delivery systems. whereas sodium cholate. an edge activator has been used as a surfactant in making ultradeformable and ultraflexible liposomes called Transfersomes. Using both a cationic lipid, DOTAP and sodium cholate. a newly formulated ultradeformable cationic liposome has been prepared. The average particle size of this formulation was approximately 80nm. (omitted)

• Bulletin of the Korean Chemical Society
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• 제24권11호
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• pp.1637-1640
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• 2003

Quaternary ammonium groups were introduced to Starburst polyamidoamine (PAMAM) dendrimers for a gene carrier. These quaternary dendritic carriers exhibited reduced cytotoxicity on 293T cells compared to parent dendrimers examined and their transfection efficiency were similar with parent dendrimers. Quaternization could be a promising tool to improve properties of dendrimers as a gene delivery carrier.

• Journal of Industrial and Engineering Chemistry
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• 제67권
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• pp.284-292
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• 2018

Receptor for advanced glycation end-products (RAGE) is overexpressed in various cancer cells. In this study, a RAGE-binding peptide (RBP) was conjugated to polyethylenimine (25 kDa, PEI). RBP-conjugated PEI (PEI-RBP) was characterized as a dual-functional reagent, a RAGE-mediated gene carrier and an anti-angiogenic reagent. As a gene carrier, PEI-RBP had higher transfection efficiency to the C6 glioblastoma cells than PEI. As an anti-angiogenic reagent, the pEmpty/PEI-RBP complex reduced RAGE expression on the surface of the C6 glioblastoma cells. Also, the complex reduced the VEGF expression and tube formation of endothelial cells. Therefore, PEI-RBP may be useful for development of glioblastoma therapy.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.226.3-227
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• 2003

A cationic lipid emulsion (o/w) containing lipiodol and 1, 2-dioleoyl-sn- glycero-3-trimethylammonium-propane (DOTAP) has been prepared as a gene delivery system. In order to increase the transfection efficiency of the lipiodol emulsion, 1 2-dioleoyl-sn-glycero-3-phospho-ethanolamine (DOPE) and polyoxyethylene sorbitan monooleate (Tween 80) were incorporated as additional lipids. By including DOPE and Tween 80, the cationic emulsion became a more potent gene carrier under in vitro condition in the presence of serum, and under in vivo condition. (omitted)

• Reproductive and Developmental Biology
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• 제35권4호
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• pp.449-455
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• 2011

Induced pluripotent stem (iPS) cells have been generated from mouse and human somatic cells by etopic expression of transcription factors. iPS cells are indistinguishable from ES cells in terms of morphology and stem cell marker expression. Moreover, mouse iPS cells give rise to chimeric mice that are competent for germline transmission. However, mice derived from iPS cells often develop tumors. Furthermore, the low efficiency of iPS cell generation is a big disadvantage for mechanistic studies. Nonviral plasmid.based vectors are free of many of the drawbacks that constrain viral vectors. The histone deacetylase inhibitor valproic acid (VPA) has been shown to improve the efficiency of mouse and human iPS cell generation, and vitamin C (Vc) accelerates gene expression changes and establishment of the fully reprogrammed state. The MEK inhibitor PD0325901 (Stemgent) has been shown to increase the efficiency of the reprogramming of human primary fibroblasts into iPS cells. In this report, we described the generation of mouse iPS cells devoid of exogenous DNA by the simple transient transfection of a nonviral vector carrying 2A-peptide-linked reprogramming factors. We used VPA, Vc, and the MEK inhibitor PD0325901 to increase the reprogramming efficiency. The reprogrammed somatic cells expressed pluripotency markers and formed EBs.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1285-1290
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• 2014

The aim was to determine whether ultrasound targeted microbubble destruction (UTMD) promotes dual targeting of HSP72 and HSC70 for therapy of castration-resistant prostate cancer (CRPC), to improve the specific and efficient delivery of siRNA, to induce tumor cell specific apoptosis, and to find new therapeutic targets specific of CRPC.VCaP cells were transfected with siRNA oligonucleotides. HSP70, HSP90 and cleaved caspase-3 expression were determined by real-time quantitative polymerase chain reaction and Western blotting. Apoptosis and transfection efficiency were assessed by flow cytometry. Cell viability assays were used to evaluate safety. We found HSP72, HSC70 and HSP90 expression to be absent or weak in normal prostate epithelial cells (RWPE-1), but uniformly strong in prostate cancerous cells (VCaP). UTMD combined with dual targeting of HSP72 and HSC70 siRNA improve the efficiency of transfection, cell uptake of siRNA, downregulation of HSP70 and HSP90 expression in VCaP cells at the mRNA and protein level, and induction of extensive tumor-specific apoptosis. Cell counting kit-8 assays showed decreased cellular viability in the HSP72/HSC70-siRNA silenced group. These results suggest that the combination of UTMD with dual targeting HSP70 therapy for PCa may be most efficacious, providng a novel, reliable, non-invasive, safe targeted approach to improve the specific and efficient delivery of siRNA, and achieve maximal effects.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2001년도 추계학술발표대회
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• pp.66-69
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• 2001

Previously we developed a CHO cell line (CHO-OTC1-A19) expressing the first two enzymes of urea cycle. This cell line showed higher ammonia removal activity and faster growth rate than the vector controlled CHO cells (CHO-neo-5). The purpose of this study was to develop a cell line with higher ammonia removal activity than the cell line developed previously. To accomplish this, we constructed stable CHO cell lines expressing the first three, the first four, or all five enzymes of urea cycle by the stable transfection method. We finally selected CHO-AL-19 cell line expressing the first three, the first four enzymes of the cycle with higher ammonia activity than CHO-OTC1-A19 and CHO-n대-5 cell lines: 40% and 15% higher than those of CHO-neo-5 and CHO-OTC1-A19 cell lines 72 hour after culture started, respectively. It also showed 44% and 10% higher cell viability than CHO-neo-5 and CHO- OTC1-A19 cell lines at higher cell density. In addition, CHO-AL-19 cells showed 45%-60% and about 20% lower ammonia concentration per cell than those of CHO-neo-% and CHO-OTC1-A19 cell lines, respectively. These results indicate that CHO-AL-19 could be used in the production of human therapeutic proteins with higher efficiency.