A novel therapeutic technology of specific RNA inhibition for acute promyelocytic leukemia: improved design of maxizymes against PML/RARalpha mRNA.

Hirotsugu Suwanai, Hiromichi Matsushita, Hiroyuki Kobayashi, Yasuo Ikeda, Masahiro Kizaki

研究成果: Article査読

6 被引用数 (Scopus)

抄録

Targeting of PML/RARalpha 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/RARalpha 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/RARalpha 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/RARalpha mRNA but not wild-type RARalpha 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.

本文言語English
ページ(範囲)127-130
ページ数4
ジャーナルInternational journal of oncology
20
1
出版ステータスPublished - 2002 1月

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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