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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Antileukemia effect of c-myc N3'-->P5' phosphoramidate antisense oligonucleotides in vivo.

In vitro, uniformly modified oligonucleotide N3'-->P5' phosphoramidates are apparently more potent antisense agents than phosphorothioate derivatives. To determine whether such compounds are also effective in vivo, severe combined immunodeficiency mice injected with HL-60 myeloid leukemia cells were treated systemically with equal doses of either phosphoramidate or phosphorothioate c-myc antisense or mismatched oligonucleotides. Compared with mice treated with mismatched oligodeoxynucleotides, the peripheral blood leukemic load of mice treated with the antisense sequences was markedly reduced, and such effects were associated with significantly prolonged survival of the antisense-treated mice. Moreover, with each of three different treatment schedules (100, 300, or 900 microg/day for 6 consecutive days), survival of the phosphoramidate-treated mice was significantly longer than that of the phosphorothioate-treated mice. Both phosphoramidate and phosphorothioate oligonucleotides were efficiently taken up by leukemic cells in vivo and were capable of specifically down-regulating c-Myc expression. Moreover, tissue distribution of the phosphoramidate derivatives was undistinguishable from that of the phosphorothioate derivatives. Collectively, these studies suggest that phosphoramidate oligonucleotides can serve as potent and specific antisense agents in the treatment of human leukemia and probably of other malignancies.[1]


  1. Antileukemia effect of c-myc N3'-->P5' phosphoramidate antisense oligonucleotides in vivo. Skorski, T., Perrotti, D., Nieborowska-Skorska, M., Gryaznov, S., Calabretta, B. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
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