A novel therapeutic technology of specific RNA inhibition for acute promyelocytic leukemia: Improved design of maxizymes against PML/RARα mRNA

  • Authors:
    • H. Suwanai
    • H. Matsushita
    • H. Kobayashi
    • Y. Ikeda
    • M. Kizaki
  • View Affiliations

  • Published online on: January 1, 2002     https://doi.org/10.3892/ijo.20.1.127
  • Pages: 127-130
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Abstract

Targeting of PML/RARα using a loss of function strategy in acute promyelocytic leukemia (APL) is a direct therapeutic approach for patients and may be the basis of future gene therapy for this leukemia. To achieve this, we designed specific maxizymes, novel allosterically controllable ribozymes, against both short and long PML/RARα isoforms. The maxizyme has sensor arms that can only recognize target sequences, and it can form a cavity that captures catalytically indispensable Mg2+. We deleted 1 base nucleotide in the Mg2+-binding pocket designed MzPRT50 and MzPRK55. The distance from the PML/RARα junction site to the center of effectors is only 2 bases, and there are 8 and 9 complementary bases in their inactive forms, respectively. Both maxizymes specifically cleaved PML/RARα mRNA but not wild-type RARα mRNA in a cell-free system. Modification of the sequence of the Mg2+-binding pocket will be important in designing the sequence-specific maxizymes against oncogenic genes.

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January 2002
Volume 20 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Suwanai H, Matsushita H, Kobayashi H, Ikeda Y and Kizaki M: A novel therapeutic technology of specific RNA inhibition for acute promyelocytic leukemia: Improved design of maxizymes against PML/RARα mRNA. Int J Oncol 20: 127-130, 2002
APA
Suwanai, H., Matsushita, H., Kobayashi, H., Ikeda, Y., & Kizaki, M. (2002). A novel therapeutic technology of specific RNA inhibition for acute promyelocytic leukemia: Improved design of maxizymes against PML/RARα mRNA. International Journal of Oncology, 20, 127-130. https://doi.org/10.3892/ijo.20.1.127
MLA
Suwanai, H., Matsushita, H., Kobayashi, H., Ikeda, Y., Kizaki, M."A novel therapeutic technology of specific RNA inhibition for acute promyelocytic leukemia: Improved design of maxizymes against PML/RARα mRNA". International Journal of Oncology 20.1 (2002): 127-130.
Chicago
Suwanai, H., Matsushita, H., Kobayashi, H., Ikeda, Y., Kizaki, M."A novel therapeutic technology of specific RNA inhibition for acute promyelocytic leukemia: Improved design of maxizymes against PML/RARα mRNA". International Journal of Oncology 20, no. 1 (2002): 127-130. https://doi.org/10.3892/ijo.20.1.127