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Potent Growth Inhibition of Leukemic Cells by Novel Ribbon-type Antisense Oligonucleotides to c-myb1

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Author(s)
Ik-Jae MoonKyusam ChoiYoung-Kook ChoiJi-Eyon KimYoungik LeeAlan D. SchreiberJong-Gu Park
Keimyung Author(s)
Park, Jong Gu
Department
Dept. of Molecular Medicine (분자의학)
Institute for Medical Science (의과학연구소)
Journal Title
Journal of Biological Chemistry
Issued Date
2000
Volume
275
Issue
7
Abstract
We studied the effects of antisense oligonucleotides
(AS oligos) with a novel structure. The AS oligos were
covalently closed to avoid exonuclease activities by enzymatic
ligation of two identical molecules. The AS oligos
of a ribbon type (RiAS oligos) consist of two loops
containing multiple antisense sequences and a stem
connecting the two loops. Three antisense sequences
targeting different binding sites were placed in a loop
that was designed to form a minimal secondary structure
by itself. RiAS oligos were found to be stable because
they largely preserved their structural integrity
after 24 h incubation in the presence of either exonuclease
III or serums. When a human promyelocytic cell line,
HL-60, was treated with RiAS oligos to c-myb, c-myb
expression was effectively ablated. Cell growth was
inhibited by >90% determined by both the 3-[4,5-dimethythiazol-
2-yl]-2,5-diphenyltetrazolium bromide assay
and [3H]thymidine incorporation. Further, when the
leukemic cell line K562 was treated with c-myb RiAS
oligos, colony formation on soft agarose was reduced by
92 6 2%. These results suggest that RiAS oligos may be
employed for developing molecular antisense drugs as
well as for the functional study of a gene.
Keimyung Author(s)(Kor)
박종구
Publisher
School of Medicine
Citation
Ik-Jae Moon et al. (2000). Potent Growth Inhibition of Leukemic Cells by Novel Ribbon-type
Antisense Oligonucleotides to c-myb1. Journal of Biological Chemistry, 275(7), 4647–4653. doi: 10.1074/jbc.275.7.4647
Type
Article
ISSN
0021-9258
DOI
10.1074/jbc.275.7.4647
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34489
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
3. Research Institutues (연구소) > Institute for Medical Science (의과학연구소)
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