• Title/Summary/Keyword: Gene delivery carrier

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Chitosan and Its Derivatives for Gene Delivery

  • Lee, Knen-Yong
    • Macromolecular Research
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    • v.15 no.3
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    • pp.195-201
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    • 2007
  • Non-viral vectors, including lipid- or polymer-based systems, have attracted much attention to date as a gene delivery vehicle, due to safety issues with viral vectors. Chitosan, a naturally existing cationic polymer, has shown great potential as a gene delivery carrier, as it has low immunogenicity and toxicity, excellent transcellular transport ability, and is relatively easy to chemically modify. This review summarizes and discusses the general features of chitosan and its applications as a delivery carrier of DNA and RNA.

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

  • Kim, Young-Min;Kim, Ji-Ho;Park, Seong-Cheol;Park, Yung-Hoon;Jang, Mi-Kyeong
    • 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.

Nonionic Amphiphilic Surfactant Conjuncted Polyethyleneimine as a New and Highly Efficient Non-viral Gene Carrier

  • Yin, Dongfeng;Chu, Cang;Ding, Xueying;Gao, Jing;Zou, Hao;Gao, Shen
    • Macromolecular Research
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    • v.17 no.1
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    • pp.19-25
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    • 2009
  • In order to enhance the gene delivery efficiency and decrease the cytotoxicity of polyplexes, we synthesized Solutol-g-PEI by conjugating polyethyleneimine (PEI) to Solutol (polyoxyethylene (10) stearate), and evaluated its efficiency as a possible nonviral gene carrier candidate. Structural analysis of synthesized polymer was performed by using $^1H$-NMR. Gel retardation assay, particle sizes and zeta potential measurement confirmed that the new gene carrier formed a compact complex with plasmid DNA. The complexes were smaller than 150 nm, which implicated its potential for intracellular delivery. It showed lower cytotoxicity in three different cell lines (Hela, MCF-7, and HepG2) than PEI 25 kDa. pGL3-lus was used as a reporter gene, and the transfection efficiency was in vitro measured in Hela cells. Solutol-g-PEI showed much higher transfection efficiency than unmodified PEI 25 kDa.

The Current Status of Adenovirus-based Cancer Gene Therapy

  • Shirakawa, Toshiro
    • 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.

Targeted Polymeric Gene Delivery for Anti-angiogenic Tumor Therapy

  • Kim, Won-Jong;Kim, Sung-Wan
    • 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.

Quaternized Polyamidoamine Dendrimers as Novel Gene Delivery System: Relationship between Degree of Quaternization and Their Influences

  • Lee, Jung-Hoon;Lim, Yong-Beom;Choi, Joon-Sig;Choi, Myung-Un;Yang, Chul-Hak;Park, Jong-Sang
    • Bulletin of the Korean Chemical Society
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    • v.24 no.11
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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.

R3V6 Amphiphilic Peptide with High Mobility Group Box 1A Domain as an Efficient Carrier for Gene Delivery

  • Ryu, Jaehwan;Jeon, Pureum;Lee, Minhyung
    • Bulletin of the Korean Chemical Society
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    • v.34 no.12
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    • pp.3665-3670
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    • 2013
  • The R3V6 peptide includes a hydrophilic arginine stretch and a hydrophobic valine stretch. In previous studies, the R3V6 peptide was evaluated as a gene carrier and was found to have low cytotoxicity. However, the transfection efficiency of R3V6 was lower than that of poly-L-lysine (PLL) in N2A neuroblastoma cells. In this study, the transfection efficiency of R3V6 was improved in combination with high mobility group box 1A domain (HMGA). HMGA is originated from the nuclear protein and has many positively-charged amino acids. Therefore, HMGA binds to DNA via charge interaction. In addition, HMGA has a nuclear localization signal peptide and may increase the delivery efficiency of DNA into the nucleus. The ternary complex with HMGA, R3V6, and DNA was prepared and evaluated as a gene carrier. First, the HMGA/DNA complex was prepared with a negative surface charge. Then, R3V6 was added to the complex to coat the negative charges of the HMGA/DNA complex, forming the ternary complex of HMGA, R3V6, and DNA. A physical characterization study showed that the ternary complex was more stable than the PLL/DNA complex. The HMGA/R3V6/DNA complex had a higher transfection efficiency than the PLL/DNA, HMGA/DNA, or R3V6/DNA complexes in N2A cells. Furthermore, the HMGA/R3V6/DNA complex was not toxic to cells. Therefore, the HMGA/R3V6/DNA complex may be a useful gene delivery carrier.

RAGE-binding peptide-conjugated polyethylenimine as a dual-functional carrier: A RAGE-mediated gene carrier and an anti-angiogenic reagent

  • Lee, Dahee;Choi, Eunji;Lee, Jaewon;Oh, Jungju;Lee, Seonyeong;Lee, Minhyung
    • Journal of Industrial and Engineering Chemistry
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    • v.67
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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.

Novel Gene Delivery Carrier Using Chitosan-Lipoic Acid Comb-Type Copolymer (키토산-리포산 빗살형 공중합체를 이용한 유전자 전달체 개발)

  • Kwon, Sang-Kyoo;Kim, Sung-Wan;Kim, Young-Jin
    • Polymer(Korea)
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    • v.34 no.6
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    • pp.501-506
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    • 2010
  • Natural chitosan has high molecular weight and the poor solubility in water. Water-soluble chitosan with low molecular weight was prepared by the hydrolysis method. In order to develop an efficient gene delivery carrier, chitosan was conjugated with lipoic acid to form the comb-type copolymer. The copolymer with the amphiphilic property formed the self-assembled nanoparticles in the aqueous solution. The average size of nanoparticles was 217.6 nm and the average size of nanoparticles/DNA complex was 170 nm. New chitosan-lipoic acid copolymer showed the low cytotoxicity and 10 times higher transfection efficiency than that of the pure chitosan.

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

  • Lee, Kyung-Man;Kim, In-Sook;Shin, Sang-Chul;Oh, In-Joon
    • Proceedings of the PSK Conference
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    • 2003.04a
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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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