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1

RNA modulation, repair and remodeling by splice switching oligonucleotides

100%
Kole R., Williams T., Cohen L.
Acta Biochimica Polonica
|
2004
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tom 51
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nr 2
Targeting splicing by antisense oligonucleotides allows RNA modifications that are not possible with RNA interference or other antisense techniques that destine the RNA for destruction. By changing the ratio of naturally occurring splice variants the expression of mRNA is modulated. By preventing the use of an aberrant splice site created by a mutation and enforcing re-selection of correct splice sites the RNA is repaired. Antisense induced skipping of the exon that carries a nonsense mutation remodels the mRNA and restores the reading frame of the defective protein. All of the above approaches have clinical applications. Modulation of splice variants is par­ticularly important since close to 60% of all genes code for alternatively spliced pre-mRNA.
2
Content available remote

Targeting clusterin in prostate cancer

75%
Rizzi F., Bettuzzi S.
Journal of Physiology and Pharmacology. Supplement
|
2008
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tom 59
|
nr 9
265-274
3

The isoform- and location-dependence of the functioning of the plasma membrane calcium pump

75%
Zylinska L., Kawecka I., Lachowicz L., Szemraj J.
Cellular and Molecular Biology Letters
|
2002
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tom 07
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nr 4
The plasma membrane is a specialised multi-component structure with inter- and intracellular signalling functions. Ca2+ plays a crucial role in cellular physiology, and an ATP-driven plasma membrane calcium pump (PMCA) plays the greatest role in the maintenance of a low free Ca2+ concentration in the cytoplasm. The enzyme is coded by four separate genes (PMCA 1-4), and, due to alternative splicing, more than 20 variants can exist. PMCA 1 and 4 isoforms are present in almost all tissues, whereas PMCA 2 and 3 are found in more specialised cell types. The variants differ primarily in their regulatory regions, thus the modulation of calcium pump activity strongly depends on the isoform and the membrane composition. The unique function of PMCA isoforms was confirmed using the practical experimental models - a rat pheochromocytoma cell line, a human neuroblastoma cell line, or, more recently, knockout mice. In addition, based on the finding that PMCA could interact with several specific signaling proteins, it was concluded that its location in defined sites of the cell membrane could be a prerequisite for efficient intercellular communication.
4

Tissue distribution of a menthyl-conjugated oligodeoxyribonucleotide antisense to PAI-1 mRNA

75%
Szemraj J., Al-Nedawi K. N. I., Chabielska E., Buczko W., Pawlowska Z.
Acta Biochimica Polonica
|
2005
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tom 52
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nr 4
The inhibitory effect of numerous analogues of PO-16, an hexadecadeoxyribonucleotide antisense to sequences -22 to -17 of PAI-1 mRNA coding for a fragment of the signal peptide, on the expression of PAI-1 in endothelial cells, and physiological consequences of the subsequently reduced PAI-1 activity tested in vitro and in vivo, were described in our previous studies. Of particular interest was PO-16 5'-O-conjugated with menthyl phosphorothioate (MPO-16R). In this work, tissue localisation of MPO-16R labelled with [35S] phosphorothioate at the 3'-end, was determined. [35S]MPO-16R and control [35S]MPO-16R-SENSE oligonucleotides were administered intravenously into 22 rats and organ distribution of the labelled bioconjugates was assessed after 24 and 48 h. For this purpose, tissue sections were subjected to autoradiography, and quantitated by liquid scintillation after solubilisation. Overall clearance of radioactivity was already seen after 24 h, with the radioactivity recovered mainly in the kidney and liver. A smaller fraction of radioactivity was also retained in the spleen and heart. The kidney concentration of the labelled probe was higher than that of liver by 50%. The distribution of PAI-1 mRNA in untreated rat kidney, liver, spleen and heart established by two independent techniques: Ribonuclease Protection Assay and Real-Time PCR, shows the same pattern as that observed for [35S]MPO-16R antisense.
5

In vitro delivery of antisense oligonucleotides

75%
Jaaskelainen I., Honkakoski P., Urtti A.
Cellular and Molecular Biology Letters
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2002
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tom 07
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nr 2
6

The effect of antisense oligonucleotide treatment of plasma membrane Ca2plus-ATPase in PC12 cells

75%
Szemraj J., Kawecka I., Bartkowiak J., Zylinska L.
Cellular and Molecular Biology Letters
|
2004
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tom 09
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nr 3
Plasma membrane Ca2+-ATPase (PMCA), encoded by four separate genes, constitutes a high affinity system extruding Ca2+ outside the cell. The nerve growth factor-treated PC12 cell line possesses all four main PMCA isoforms. To evaluate the potential role of PMCA isoforms in the differentiation process, we transiently suppressed the expression of PMCA2 and 3 using the antisense oligonucleotides. In the transfected PC12 cells, we observed morphological changes, slowed neurite extension and diminished survival of the cells. The apparent transport activity and affinity of the calcium pump to Ca2+ were lower in the cells with suppressed PMCA2 and 3 isoforms than in the control cells. Moreover, in the transfected PC12 plasma membranes, the calcium pump was insensitive to stimulation by calmodulin. These findings suggest that PMCA2 and 3 isoforms may be involved in developmental and differentiation processes.
7

Apoptosis monitoring in human acute leukaemia cells stimulated by Bcl-2 antisense oligonucleotide and BAY K 8644

63%
Kocki J., Kocki T., Lancut M., Bogucka-Kocka A., Cioch M., Dmoszynska A., Wojcierowski J.
Polish Journal of Environmental Studies
|
2004
|
tom 13
|
nr Suppl.2, Part 1
In this study we investigated effects of bcl-2 antisense oligonucleotides (AS) and BAY K 8644 (B), calcium channel agonist, on human leukaemic cells from non-treatment patients with acute myeloblastic leukaemias. Apoptotic cells were observed in electron and fluorescent microscopes. When we examined the effects of AS + B on cells, level of bcl-2 mRNA decreased more as in cells stimulated by AS only. These observations indicate that AS with B in human leukaemic cells disturb cell viability by inducing apoptosis.
8
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Content available

A primary attempt of Leptinotarsa decemlineata control using contact DNA insecticide based on short antisense oligonucleotide of its CYP6B gene

63%
Oberemok V., Laikova K., Shumskykh M., Kenyo I., Kasich I., Deri K., Seidosmanova E., Krasnodubets A., Bekirova V., Gal'chinsky N.
Journal of Plant Protection Research
|
2018
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tom 58
|
nr 1
Effective control of Leptinotarsa decemlineata remains an urgent problem for agriculture worldwide. Minimization of the use of non-selective neonicotinoid insecticides, such as thiomethoxam, is an actual vector of development of potato cultivation. In this rapid communication, we show the prospect of the topical use of short unmodified antisense fragment of L. decemlineata CYP6B gene as a DNA insecticide. Investigated parameters, namely, number of larvae per plant, aboveground biomass, yield and number of potatoes produced per plant indicate the possibility of this post-genomic approach as a safe and effective method of L. decemlineata control.
9

Antisense protein kinase A RIalpha-induced tumor reversion: portrait of a microarray

63%
Cho-Chung Y. S.
Cellular and Molecular Biology Letters
|
2003
|
tom 08
|
nr 2A
10

Modification of pre-mRNA splicing by antisense oligonucleotides

63%
Kole R.
Acta Biochimica Polonica
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1997
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tom 44
|
nr 2
Antisene oligonucleotides have been extensively studied as agents that inhibit the expression of undesirable genes in a sequence specific manner. Results reviewed in this article show that antisene oligonucleotides can also restore the expression of genes inactivated by mutations causing genetic diseases. In this novel application, antisene oligonucleotides block aberrant splice sites created by the mutations, forcing the spliceosomes to form at correct splice sites, thus restoring the proper splicing pathway and consequently the activity of the damaged gene.
11
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Content available

The role of dopamine D2 receptor in the behavioral effects of imipramine - study with the use of antisense oligonucleotides

63%
Dziedzicka-Wasylewska M., Kolasiewicz W., Rogoz Z., Margas W., Maj J.
Journal of Physiology and Pharmacology
|
2000
|
tom 51
|
nr 3
12

Multidrug resistance-associated protein - reduction of expression in human leukaemia cells by antisense phosphorothioate oligonucleotides

63%
Niewiarowski W., Gendaszewska E., Rebowski G., Wojcik M., Mikolajczyk B., Goos W., Soszynski M., Bartosz G.
Acta Biochimica Polonica
|
2000
|
tom 47
|
nr 4
Multidrug resistance-associated protein (MRP1) causes cellular drug resistance in several cancer cell lines. In this paper we show that antisense oligonucleotides decrease MRP1 expression in human leukaemia cells. We investigated biological activity of a series of 12 linear phosphorothioate oligonucleotides, complementary to several regions of MRP1 mRNA. The oligonucleotides were administered to leukaemia HL60/ADR cells overexpressing MRP1 protein. Then, the level of MRP1 mRNA was determined by means of semiquantitative RT-PCR and the protein level by reaction with specific monoclonal antibodies. Some of the investigated antisense oligonucleotides decrease the expression level of the MRP1 protein by 46% and its mRNA level by 76%.
13

Proprotein convertase subtilisin/kexin type 9: A new target molecule for gene therapy

51%
Banaszewska A., Piechota M., Plewa R.
Cellular and Molecular Biology Letters
|
2012
|
tom 17
|
nr 2
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a novel target for controlling plasma levels of low-density lipoprotein cholesterol (LDL-C) and decreasing the risk of cardiovascular diseases. At present it is clear that the major classes of commonly prescribed lipid-lowering medications increase serum PCSK9 levels and fail to protect a significant percentage of patients from cardiovascular events. Therefore development of new LDL-C lowering medications that either do not increase circulating PCSK9 levels or work through inhibition of PCSK9 expression and protease activity is a highly desirable approach to overcome hypercholesterolemia. Since there are several agents which are being evaluated in human preclinical and clinical trials, this review summarizes current therapeutic strategies targeting PCSK9, including specific antibodies, antisense oligonucleotides, small interfering RNAs (siRNAs) and other small-molecule inhibitors.
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