Target site search and effective inhibition of leukaemic cell growth by a covalently closed multiple anti-sense oligonucleotide to c-myb

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dc.contributor.authorIk Jae Moon-
dc.contributor.authorYoung Ik Lee-
dc.contributor.authorChun Sik Kwak-
dc.contributor.authorJe Ho Lee-
dc.contributor.authorKyu Sam Choi-
dc.contributor.authorAlan D Schreiber-
dc.contributor.authorJong Gu Park-
dc.date.accessioned2017-04-19T08:56:57Z-
dc.date.available2017-04-19T08:56:57Z-
dc.date.issued2000-
dc.identifier.issn0264-6021-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/5048-
dc.description.abstractSystematic secondary structure simulation of a target mRNA sequence is shown to be effective for locating a good anti-sense target site. Multiple selected anti-sense sequences were placed in a single molecule. The anti-sense oligonucleotide (oligo) was covalently closed to avoid exonuclease activities and was designated CMAS (covalently closed multiple anti-sense)-oligo. CMAS-oligo was found to be stable, largely preserving its structural integrity after 24 h of incubation in the presence of either exonuclease III or serum. When human c-myb mRNA was targeted by the c-myb CMAS-oligo, expression of the gene was completely abolished. Further, tumour cell growth was inhibited by 82 ± 3% as determined by an MTT [3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay and by 90 ± 1% by [3H]thymidine incorporation. When a leukaemic cell line K562 was treated with CMAS-oligo, colony formation on soft agarose was also decreased by 93%. In contrast, treatment with a scrambled control oligo did not significantly inhibit leukaemic cell growth. These results suggest that a rational target site search is possible for an anti-sense oligo and that CMAS-oligo can be employed as an effective anti-sense agent with enhanced stability.-
dc.publisherPortland Press Ltd-
dc.titleTarget site search and effective inhibition of leukaemic cell growth by a covalently closed multiple anti-sense oligonucleotide to c-myb-
dc.title.alternativeTarget site search and effective inhibition of leukaemic cell growth by a covalently closed multiple anti-sense oligonucleotide to c-myb-
dc.typeArticle-
dc.citation.titleBiochemical Journal-
dc.citation.number2-
dc.citation.endPage303-
dc.citation.startPage295-
dc.citation.volume346-
dc.contributor.affiliatedAuthorYoung Ik Lee-
dc.contributor.alternativeName문익재-
dc.contributor.alternativeName이영익-
dc.contributor.alternativeName곽춘식-
dc.contributor.alternativeName이재호-
dc.contributor.alternativeName최규삼-
dc.contributor.alternativeNameSchreiber-
dc.contributor.alternativeName박종구-
dc.identifier.bibliographicCitationBiochemical Journal, vol. 346, no. 2, pp. 295-303-
dc.identifier.doi10.1042/0264-6021:3460295-
dc.subject.keywordc-myb-
dc.subject.keywordgrowth inhibition-
dc.subject.keywordoligonucleotide stability-
dc.subject.localc-myb-
dc.subject.localGrowth Inhibition-
dc.subject.localgrowth inhibition-
dc.subject.localGrowth inhibition-
dc.subject.localoligonucleotide stability-
dc.description.journalClassY-
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