Published in: J. Biol. Chem., Vol. 275, Issue 7, pp. 4647-4653, (February 18, 2000):

Ik-Jae Moon ¹, Kyusam Choi ¹, Young-Kook Choi ¹, Ji-Eyon Kim ¹, Youngik Lee ², Alan D. Schreiber ³, and Jong-Gu Park ¹.

¹ Institute for Medical Science, Keimyung University Dongsan Medical Center, 194 Dongsandong, Joonggu, Taegu 700-712, South Korea,
² Molecular Cell Biology Research Division, Korea Research Institute of Bioscience and Biotechnology, Taejon 305-606, South Korea, and the
³ University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104.

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.

Additional Reference:

1. Frenster JH, "Oncogenes as Molecular Targets within Active Chromatin".