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EWS/Fli-1を標的としたリボザイムのユーイング肉腫におよぼす効果：大野貴敏¹,武内章二¹,清水克時¹,杉江茂幸²,森秀樹²,神津知子³（¹岐阜大・医・整形,²同1病理,³埼玉がんセ・研）

Effects on Ewing's sarcoma cells of chimeric DNA/RNA hammerhead ribozymes to be targeted against EWS/Fli-1 mRNA : Takatoshi OHNO^1,Shoji TAKEUCHI¹,Katsuji SHIMIZU¹,Shigeyuki SUGIE²,Hideki MORI²,Tomoko KOZU³(¹Dept. of Orthop. Surg. and ²Dept. of Pathol.,Gifu Univ. Sch. Med.,³Saitama Cancer Center Res. Inst.)

For therapeutic purposes, two chimeric DNA/RNA hammerhead ribozymes (Rz1 and Rz2) were synthesized to cleave EWS/Fli-1, the t (11;22)-associated fusion mRNA of Ewing's sarcoma and primitive neuroectodermal tumor. Both ribozymes recognize the area adjacent to the fusion point between EWS and Fli-1. Rz1 and Rz2 were synthesized to cleave 7 and 16 bases downstream from this point respectively, and both ribozymes cleaved synthetic chimeric DNA/RNA substrates at theoretical sites. Also, both cleaved the EWS/Fli-1 RNA which was synthesized in vitro transcription. The two ribozymes showed growth inhibition of Ewing's sarcoma cell line TC-135 carrying t(11;22). The growth inhibition rates of the ribozymes were greater than those of the　antisense oligonucleotides against EWS/Fli-1. The results suggest that the ribozyme has the potential to be developed as a useful agent for gene therapy for Ewing's sarcoma and primitive neuroectodermal tumor with t(11;22).