Restoration of protein synthesis in pancreatic cancer cells by trans-splicing ribozymes.
This report describes the use of trans-splicing ribozymes to restore p16 protein synthesis in pancreatic cancer cells. A group I intron ribozyme was designed to trans-splice the 2 base-deleted p16 transcripts with the wild-type sequence in a pancreatic cancer cell line, which originally produced no p16. Following transfection of the ribozyme construct in AsPC-1 cells, mutant p16 mRNA molecules were repaired and p16 protein synthesis restored. Moreover, these cells exhibited a reduced ability to grow, compared to the untransfected cells. The technology of ribozymes offers an advantage over gene replacement therapy because it maintains the cellular regulation of gene expression. These results indicate that group I intron ribozymes might prove useful towards the therapy of pancreatic cancer and in conjunction with the advancement of powerful delivery systems this technology will play a major role in the therapy of many diseases.
Kastanos
Evdokia
E
The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus.
Hjiantoniou
Eleni
E
Phylactou
Leonidas A
LA
D000818:Animals; D045744:Cell Line, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D007700:Kinetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D016337:RNA, Catalytic / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D017384:Sequence Deletion; D013768:Tetrahymena / Q000235:genetics; D014158:Transcription, Genetic
D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D016337:RNA, Catalytic; D012333:RNA, Messenger