Evaluating the specificity of antisense oligonucleotide conjugates. A DNA array analysis
Antisense oligonucleotides are potentially powerful tools for selective control of cellular and viral gene expression. Crucial to successful application of this approach is the specificity of the oligonucleotide for the chosen RNA target. Here we apply DNA array technology to examine the specificity...
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| Veröffentlicht in: | The Journal of biological chemistry 2002-06, Vol.277 (25), p.22980-22984 |
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| container_issue | 25 |
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| container_title | The Journal of biological chemistry |
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| creator | Fisher, Anna Astriab Ye, Dongjiu Sergueev, Dimitri S Fisher, Michael H Shaw, Barbara Ramsay Juliano, Rudolph L |
| description | Antisense oligonucleotides are potentially powerful tools for selective control of cellular and viral gene expression. Crucial to successful application of this approach is the specificity of the oligonucleotide for the chosen RNA target. Here we apply DNA array technology to examine the specificity of antisense oligonucleotide treatments. The molecules used in these studies consisted of phosphorothioate oligomers linked to the Antennapedia (Ant) delivery peptide. The antisense oligonucleotide component was complementary to a site flanking the AUG of the MDR1 message, which codes for P-glycoprotein, a membrane ATPase associated with multidrug resistance in tumor cells. Using a DNA array of 2059 genes, we analyzed cellular responses to molecules comprised of Ant peptide-oligonucleotide conjugates, as well as to the Ant peptide alone. Besides the expected reduction in MDR1 message level, 37 other genes (approximately 2% of those tested) showed changes of comparable magnitude. The validity of the array results was confirmed for selected genes using Northern blots to assess messenger RNA levels. These results suggest that studies using antisense oligonucleotide technology to modulate gene expression need to be interpreted with caution. |
| doi_str_mv | 10.1074/jbc.M203347200 |
| format | Article |
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The antisense oligonucleotide component was complementary to a site flanking the AUG of the MDR1 message, which codes for P-glycoprotein, a membrane ATPase associated with multidrug resistance in tumor cells. Using a DNA array of 2059 genes, we analyzed cellular responses to molecules comprised of Ant peptide-oligonucleotide conjugates, as well as to the Ant peptide alone. Besides the expected reduction in MDR1 message level, 37 other genes (approximately 2% of those tested) showed changes of comparable magnitude. The validity of the array results was confirmed for selected genes using Northern blots to assess messenger RNA levels. 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A DNA array analysis</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Antisense oligonucleotides are potentially powerful tools for selective control of cellular and viral gene expression. Crucial to successful application of this approach is the specificity of the oligonucleotide for the chosen RNA target. Here we apply DNA array technology to examine the specificity of antisense oligonucleotide treatments. The molecules used in these studies consisted of phosphorothioate oligomers linked to the Antennapedia (Ant) delivery peptide. The antisense oligonucleotide component was complementary to a site flanking the AUG of the MDR1 message, which codes for P-glycoprotein, a membrane ATPase associated with multidrug resistance in tumor cells. Using a DNA array of 2059 genes, we analyzed cellular responses to molecules comprised of Ant peptide-oligonucleotide conjugates, as well as to the Ant peptide alone. Besides the expected reduction in MDR1 message level, 37 other genes (approximately 2% of those tested) showed changes of comparable magnitude. The validity of the array results was confirmed for selected genes using Northern blots to assess messenger RNA levels. These results suggest that studies using antisense oligonucleotide technology to modulate gene expression need to be interpreted with caution.</description><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism</subject><subject>Base Sequence</subject><subject>Blotting, Northern</subject><subject>Down-Regulation</subject><subject>Flow Cytometry</subject><subject>Humans</subject><subject>Molecular Sequence Data</subject><subject>Oligonucleotide Array Sequence Analysis - methods</subject><subject>Oligonucleotides, Antisense - chemistry</subject><subject>Oligonucleotides, Antisense - metabolism</subject><subject>Oligonucleotides, Antisense - pharmacology</subject><subject>Peptides - chemistry</subject><subject>Protein Binding</subject><subject>RNA - metabolism</subject><subject>Tumor Cells, Cultured</subject><issn>0021-9258</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkL1PwzAUxD2AaCmsjMgTW4KfndTJWJXyIRVYQGKLXuyX4ipNQuwg5b8nEmXmbrjldzccY1cgYhA6ud2XJn6WQqlESyFO2FwICVEu02zGzr3fi0lJDmdsBpAnGeTpnH1svrEeMLhmx8Mncd-RcZUzLoy8rTg2wXlqPPG2dru2GUxNbXCWuGmb_bDDQD7mK373suLY9zhODaxH7_wFO62w9nR5zAV7v9-8rR-j7evD03q1jTqpshAhVaXSRpciNcqWukxtolFpJbStlAUwWlMqBQoNBpAyUEpI1LlZQpZaqxbs5ne369uvgXwoDs4bqmtsqB18oSFTsMzzf0HIEhCTJ_D6CA7lgWzR9e6A_Vj8naZ-AD8_bQ0</recordid><startdate>20020621</startdate><enddate>20020621</enddate><creator>Fisher, Anna Astriab</creator><creator>Ye, Dongjiu</creator><creator>Sergueev, Dimitri S</creator><creator>Fisher, Michael H</creator><creator>Shaw, Barbara Ramsay</creator><creator>Juliano, Rudolph L</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20020621</creationdate><title>Evaluating the specificity of antisense oligonucleotide conjugates. 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A DNA array analysis</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2002-06-21</date><risdate>2002</risdate><volume>277</volume><issue>25</issue><spage>22980</spage><epage>22984</epage><pages>22980-22984</pages><issn>0021-9258</issn><abstract>Antisense oligonucleotides are potentially powerful tools for selective control of cellular and viral gene expression. Crucial to successful application of this approach is the specificity of the oligonucleotide for the chosen RNA target. Here we apply DNA array technology to examine the specificity of antisense oligonucleotide treatments. The molecules used in these studies consisted of phosphorothioate oligomers linked to the Antennapedia (Ant) delivery peptide. The antisense oligonucleotide component was complementary to a site flanking the AUG of the MDR1 message, which codes for P-glycoprotein, a membrane ATPase associated with multidrug resistance in tumor cells. Using a DNA array of 2059 genes, we analyzed cellular responses to molecules comprised of Ant peptide-oligonucleotide conjugates, as well as to the Ant peptide alone. Besides the expected reduction in MDR1 message level, 37 other genes (approximately 2% of those tested) showed changes of comparable magnitude. The validity of the array results was confirmed for selected genes using Northern blots to assess messenger RNA levels. These results suggest that studies using antisense oligonucleotide technology to modulate gene expression need to be interpreted with caution.</abstract><cop>United States</cop><pmid>11948195</pmid><doi>10.1074/jbc.M203347200</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism Base Sequence Blotting, Northern Down-Regulation Flow Cytometry Humans Molecular Sequence Data Oligonucleotide Array Sequence Analysis - methods Oligonucleotides, Antisense - chemistry Oligonucleotides, Antisense - metabolism Oligonucleotides, Antisense - pharmacology Peptides - chemistry Protein Binding RNA - metabolism Tumor Cells, Cultured |
| title | Evaluating the specificity of antisense oligonucleotide conjugates. A DNA array analysis |
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