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

Authors
Ik-Jae MOONYoungik LEE‹Chun-Sik KWAKJe-Ho LEEŒKyusam CHOIAlan D. SCHREIBERJong-Gu PARK
Department
Dept. of Biochemistry (생화학); Dept. of Molecular Medicine (분자의학); Institute for Medical Science (의과학연구소)
Issue Date
2000
Citation
Biochemical Journal, Vol.346(2) : 295-303, 2000
ISSN
0264-6021
Abstract
Systematic 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 82³3%as determined by an MTT [3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay and by 90³1%by [$H]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 signi®cantly inhibit leukaemic cell growth. These results suggest that a rational target site search is possible for an anti-sense oligo and that CMASoligo can be employed as an effective anti-sense agent with enhanced stability. Key words: c-myb, growth inhibition, oligonucleotide stability.
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/33698
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Biochemistry (생화학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
1. Journal Papers (연구논문) > 3. Research Institutues (연구소) > Institute for Medical Science (의과학연구소)
Keimyung Author(s)
곽춘식; 박종구
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