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      Antisense Oligonucleotides

      , ,

      Cardiorenal Medicine

      S. Karger AG

      Antisense oligonucleotides, Gene therapy, Liposomes

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          Antisense technology was developed to inhibit gene expression by utilizing an oligonucleotide complementary to the mRNA which encodes the target gene. There are a few possible mechanisms for the inhibitory effects of antisense oligonucleotides. Among them, degradation of mRNA by RNase H is considered to be the major mechanism of action for antisense oligonucleotides. This technique was originally used to elucidate the function of a target gene, but may also have therapeutic applications, provided it is designed carefully and properly.

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          Most cited references 2

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          Cytoplasmic domains of the interleukin-2 receptor beta and gamma chains mediate the signal for T-cell proliferation.

          The interleukin-2 receptor (IL-2R) consists of three distinct chains (alpha, beta, gamma) which bind IL-2 and generate a proliferative signal in T cells. To define the mechanism of receptor activation, chimaeric receptors were constructed from the intracellular region of either IL-2R beta or IL-2R gamma and the extracellular region of c-kit, a receptor tyrosine kinase that homodimerizes on binding stem cell factor (SCF). We report here that binding of SCF to the beta-chain chimaera induced proliferation of the pro-B-cell line BA/F3, but not T cells. But in T cells expressing both the beta- and gamma-chain chimaeras, SCF induced proliferation and tyrosine phosphorylation characteristic of the native IL-2R signal. Chimaeric IL-2 receptor beta and gamma chains constructed with the heterodimeric extracellular regions of the granulocyte-macrophage colony stimulating factor receptor (GM-CSFR) also provided the IL-2R signal. Thus, heterodimerization of the cytoplasmic domains of IL-2R beta and -gamma appears necessary and sufficient for signalling in T cells.
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            Efficient gene transfer with less cytotoxicity by means of cationic multilamellar liposomes.

             K Yagi,  H Noda,  M Kurono (1993)
            A simple procedure for the preparation of cationic multilamellar vesicles (MLV) consisting of N-(alpha-trimethylammonioacetyl)-didodecyl-D-glutamate chloride, dilauroyl phosphatidylcholine, and dioleoyl phosphatidylethanolamine in a molar ratio of 1:2:2 was devised. When bacteriophage lambda DNA was encapsulated into these liposomes, entrapment efficiency was found to be nearly 100%, and digestibility of the DNA was less than 10%. Upon encapsulation of the plasmid pCH110 into cationic MLV, efficient expression was comparable to that obtained with cationic vesicles prepared by reverse-phase evaporation method (REV). Cytotoxicity of the present liposomes was less than that of cationic REV and far less than that of Lipofectin.

              Author and article information

              Nephron Exp Nephrol
              Cardiorenal Medicine
              S. Karger AG
              February 1998
              04 February 1998
              : 6
              : 1
              : 84-88
              Department of Medicine III, Okayama University Medical School, Okayama, Japan
              20509 Exp Nephrol 1998;6:84–88
              © 1998 S. Karger AG, Basel

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              Page count
              Figures: 1, Tables: 1, References: 30, Pages: 5
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              Technical Seminar:Strategies for Functional Inactivation of Genes

              Cardiovascular Medicine, Nephrology

              Antisense oligonucleotides, Liposomes, Gene therapy


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