Tumor-specific gene delivery using RNA-targeting Tetrahymena group I intron.
Current gene therapy protocols against cancer often have limited target specificity. Here, a novel tumor-specific targeted gene delivery procedure, which is based on Tetrahymena group I intron ribozyme, is presented. This ribozyme can target a cancer-specific transcript and then replace the RNA with new transcripts, resulting in induction of the transgene activity selectively in cancer cells that express the target RNA. The RNA replacement occurs by trans-splicing reaction with high fidelity with the target RNA. In addition, the ribozyme can specifically inhibit function of the targeted gene in the cells expressing the RNA. Moreover, the ribozyme can selectively deliver cytotoxin gene activity into cancer cells expressing the RNA and thereby specifically hampers the survival of these cells. These findings suggest that the trans-splicing ribozyme that targets the cancer-specific RNA could be a potential agent for specific tumor gene therapy.
Jung
Heung-Su
HS
Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Seoul, 140-714, Korea.
Kwon
Byung-Su
BS
Lee
Seong-Wook
SW
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D016373:DNA, Antisense / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018390:Gene Targeting / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007438:Introns / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D016337:RNA, Catalytic / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D013768:Tetrahymena / Q000235:genetics*; D014162:Transfection
D016373:DNA, Antisense; D004268:DNA-Binding Proteins; D016337:RNA, Catalytic; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D019098:Telomerase