• 제목/요약/키워드: Non-viral gene delivery

검색결과 42건 처리시간 0.022초

Enhancement of Gene Delivery to Cancer Cells by a Retargeted Adenovirus

  • Oh Kwang Seok;Engler Jeffrey A.;Joung In Sil
    • Journal of Microbiology
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    • 제43권2호
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    • pp.179-182
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    • 2005
  • The inefficiency of in vivo gene transfer using currently available vectors reflects a major hurdle in cancer gene therapy. Both viral and non-viral approaches that improve gene transfer efficiency have been described, but suffer from a number of limitations. Herein, a fiber-modified adenovirus, carrying the small peptide ligand on the capsid, was tested for the delivery of a transgene to cancer cells. The fiber-modified adenovirus was able to mediate the entry and expression of a $\beta$-galactosidase into cancer cells with increased efficiency compared to the unmodified adenovirus. Particularly, the gene transfer efficiency was improved up to 5 times in OVCAR3 cells, an ovarian cancer cell line. Such transduction systems hold promise for delivering genes to transferrin receptor overexpressing cancer cells, and could be used for future cancer gene therapy.

양이온 펩타이드가 컨쥬게이트된 수용성 키토산의 유전자 전달체로서의 특성 (Characteristic as a Gene Delivery System of Water Soluble Chitosan Conjugated with Cationic Peptide)

  • 김영민;김지호;박성철;박영훈;장미경
    • KSBB Journal
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    • 제31권4호
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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.

Macromolecular Cytosolic Delivery: Cell Membranes as the Primary Obstacle

  • Larson, Gretchen M.;Lee, Kyung-Dall
    • Archives of Pharmacal Research
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    • 제21권6호
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    • pp.621-628
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    • 1998
  • The "evolution" of a thing, a custom, an organ is thus by no means its progressus toward a goal, even less a logical progressus by the shortest route and with the least expendit ure of force, but a succession of more or less profound, mutually independent processes of subduing, plus the resistances they encounter, the attempts at transformation for the purpose of defense and reaction, and the results of successful counteractions. The form is fluid, but the "meaning" is even more so (Friedrich W. Nietzsche).

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신약전달기술체계인 유전자 치료의 현재까지의 개발동향 (Current Status of Gene Therapy as a New Drug Delivery System)

  • 배윤성;조정윤;지상미;이영주
    • 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.

Synthesis and characterization of transferrin-polyethylenimine conjugate for targeted gene delivery

  • Lee, Kyung-Man;Kim, In-Sook;Shin, Sang-Chul;Oh, In-Joon
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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    • pp.315.2-316
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    • 2003
  • Polyethylenimine (PEI) has been used as a non-viral gene delivery carrier. To improve the efficacy of transfection, transferrin was incorporated by covalent linkage to PEI. As a model plasmid DNA, pHME185/b-gal, a mammalian expression vector was used. The transferrin-polyethylenimine (TfPEI) was synthesized by conjugate PEI with transferrin using sodium periodateand and characterized by FT-IR and 1H-NMR. (omitted)

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Current advances in adenovirus nanocomplexes: more specificity and less immunogenicity

  • Kang, Eun-Ah;Yun, Chae-Ok
    • BMB Reports
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    • 제43권12호
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    • pp.781-788
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    • 2010
  • An often overlooked issue in the field of adenovirus (Ad)-mediated cancer gene therapy is its limited capacity for effective systemic delivery. Although primary tumors can be treated effectively with intralesional injection of conventional Ad vectors, systemic metastasis is difficult to cure. Systemic administration of conventional naked Ads leads to acute accumulation of Ad particles in the liver, induction of neutralizing antibody, short blood circulation half-life, non-specific biodistribution in undesired organs, and low selective accumulation in the target disease site. Versatile strategies involving the modification of viral surfaces with polymers and nanomaterials have been designed for the purpose of maximizing Ad anti-tumor activity and specificity by systemic administration. Integration of viral and non-viral nanomaterials will substantially advance both fields, creating new concepts in gene therapeutics. This review focuses on current advances in the development of smart Ad hybrid nanocomplexes based on various design-based strategies for optimal Ad systemic administration.

저분자량 수용성 키토산을 이용한 동맥 벽 표적성 유전자 전달체의 합성 (The Synthesis of Artery Wall Targeted Gene Carrier Using Low Molecular Water-Soluble Chitosan)

  • 최창용;장미경;나재운
    • 폴리머
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    • 제30권4호
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    • pp.279-285
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    • 2006
  • 유전자 치료에 있어서 안전성의 장점을 지니고 있는 비바이러스성 전달체에 대한 관심도가 높아져가고 있다. 비바이러스성 전달체 중, 양이온성 리포좀이나 합성 유전자 전달체는 in vitro계에서 효율적인 DNA 전달체이지만, 낮은 생체적합성으로 인하여 in vivo 계에서의 응용성은 크게 뒤떨어지고 있다. 한편, 천연 양이온성 다당류인 키토산은 낮은 독성과 강한 양전하를 띠고 있어 유전자 전달 시스템 (gene delivery system)에 있어 아주 기대되는 전달체이다. 본 연구에서는 저분자량 수용성 키토산 (low molecular water-soluble chitosan ; LMWSC)을 이용하여 동맥 벽 세포를 표적할 수 있는 표적성 유전자 전달체를 합성하였다. 상대 점도와 Kina 적정법을 이용하여 LMWSC의 점도 평균 분자량 $(M_W)$과 탈아세틸화도 (degree of de acetylation ; DDA)를 측정하였고 구조는 FTIR, $^1H-NMR$, 그리고 $^{13}C-NMR$을 통하여 분석하였다. 동맥 벽을 표적하기 위한 유전자 전달체로서 pegylated LMWSC 의 말단에 특이성 세포 표적 펩타이드인 artery wall binding peptide (AWBP)를 결합시킴으로써 AWBP-PEG-g-LMWSC을 합성하였고 FTIR, $^1H-NMR$. zeta potentiometer. 그리고 atomic force microscopy (AFM)을 이용하여 분석하였다.

New paradigms on siRNA local application

  • Pan, Meng;Ni, Jinwen;He, Huiming;Gao, Shan;Duan, Xiaohong
    • BMB Reports
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    • 제48권3호
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    • pp.147-152
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    • 2015
  • Small interfering RNA (siRNA) functions through pairing with specific mRNA sequences and results in the mRNA's degradation. It is a potential therapeutic approach for many diseases caused by altered gene expression. The delivery of siRNA is still a major problem due to its rapid degradation in the circulation. Various strategies have been proposed to help with the cellular uptake of siRNA and short or small hairpin RNA (shRNA). Here, we reviewed recently published data regarding local applications of siRNA. Compared with systemic delivery methods, local delivery of siRNA/shRNA has many advantages, such as targeting the specific tissues or organs, mimicking a gene knockout effect, or developing certain diseases models. The eye, brain, and tumor tissues are 'hot' target tissues/organs for local siRNA delivery. The siRNA can be delivered locally, in naked form, with chemical modifications, or in formulations with viral or non-viral vectors, such as liposomes and nanoparticles. This review provides a comprehensive overview of RNAi local administration and potential future applications in clinical treatment.

Antibody-secreting macrophages generated using CpG-free plasmid eliminate tumor cells through antibody-dependent cellular phagocytosis

  • Cha, Eun Bi;Shin, Keun Koo;Seo, Jinho;Oh, Doo-Byoung
    • BMB Reports
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    • 제53권8호
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    • pp.442-447
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    • 2020
  • The non-viral delivery of genes into macrophages, known as hard-to-transfect cells, is a challenge. In this study, the microporation of a CpG-free and small plasmid (pCGfd-GFP) showed high transfection efficiency, sustainable transgene expression, and good cell viability in the transfections of Raw 264.7 and primary bone marrow-derived macrophages. The non-viral method using the pCGfd vector encoding anti-EGFR single-chain Fv fused with Fc (scFv-Fc) generated the macrophages secreting anti-EGFR scFv-Fc. These macrophages effectively phagocytized tumor cells expressing EGFR through the antibody-dependent mechanism, as was proved by experiments using EGFR-knockout tumor cells. Finally, peri-tumoral injections of anti-EGFR scFv-Fc-secreting macrophages were shown to inhibit tumor growth in the xenograft mouse model.

Transfection Property of a New Cholesterol-Based Cationic Lipid Containing Tri-2-Hydroxyethylamine as Gene Delivery Vehicle

  • Kim, Bieong-Kil;Doh, Kyung-Oh;Hwang, Guen-Bae;Seu, Young-Bae
    • Journal of Microbiology and Biotechnology
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    • 제22권6호
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    • pp.866-871
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    • 2012
  • A novel cholesterol-based cationic lipid containing a tri-2-hydroxyethylamine head group and ether linker (Chol-THEA) was synthesized and examined as a potent gene delivery vehicle. In the preparation of cationic liposome, the addition of DOPE as helper lipid significantly increased the transfection efficiency. To find the optimum transfection efficiency, we screened various weight ratios of DOPE and liposome/DNA (N/P). The best transfection efficiency was found at the Chol-THEA:DOPE weight ratio of 1:1 and N/P weight ratio of 10~15. Most of the plasmid DNA was retarded by this liposome at the optimum N/P weight ratio of 10. The transfection efficiency of Chol-THEA liposome was compared with DOTAP, Lipofectamine, and DMRIE-C using the luciferase assay and GFP expression. Chol-THEA liposome with low toxicity had better or similar potency of gene delivery compared with commercial liposomes in COS-7, Huh-7, and MCF-7 cells. Therefore, Chol-THEA could be a useful non-viral vector for gene delivery.