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Title 

Potent growth inhibition of leukemic cells by novel ribbon-type antisense oligonucleotides to c-myb1

Authors 

Ik Jae MoonKyu Sam ChoiYoung Kook ChoiJi Eyon KimYoung Ik LeeAlan D SchreiberJong Gu Park

Publisher 

American Society for Biochemistry and Molecular Biology

Issue Date 

2000

Citation 

Journal of Biological Chemistry, vol. 275, no. 7, pp. 4647-4653

Keywords 

antisense oligonucleotideexonucleasecancer inhibitioncell strain HL 60enzyme activityhuman cellleukemia cellnucleotide sequenceoncogene c myboncogene c myc

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 ± 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.

ISSN 

0021-9258

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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