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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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Affiliated Author(s)
곽춘식박종구
Alternative Author(s)
Kwak, Chun SikPark, Jong Gu
Journal Title
Biochemical Journal
ISSN
0264-6021
Issued Date
2000
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.
Department
Dept. of Biochemistry (생화학)
Dept. of Molecular Medicine (분자의학)
Institute for Medical Science (의과학연구소)
Publisher
School of Medicine
Citation
Ik-Jae MOON et al. (2000). Target site search and effective inhibition of leukaemic cell growth by a
covalently closed multiple anti-sense oligonucleotide to c-myb. Biochemical Journal, 346(2), 295–303. doi: 10.1042/bj3460295
Type
Article
ISSN
0264-6021
DOI
10.1042/bj3460295
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33698
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Biochemistry (생화학)
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
3. Research Institutues (연구소) > Institute for Medical Science (의과학연구소)
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