title: Multi-unit anti-BCR-ABL ribozyme therapy in chronic myelogenous leukemia.
abstract: In this review, we summarize and update our data on the development of a multi-unit anti-BCR/ABL ribozyme. In vitro studies comparing several anti-BCR/ABL ribozymes demonstrated that a triple-unit ribozyme is the most efficient. Detailed kinetic analysis revealed this ribozyme to have a lower Kcat, most likely due to non homologous bases at restriction enzyme sites used in ribozyme construction. Delivery of this ribozyme to a BCR/ABL transformed cell line by a novel vehicle targeting the folate receptor resulted in a 3 log reduction in BCR/ABL mRNA when analyzed by RT-PCR. This delivery strategy reversed the IL-3 independence of this cell line. Retroviral vectors containing genes coding for the multi-unit ribozyme have been constructed and their use to effect BCR/ABL transformed cell biology is discussed.
authors.affiliation: Temple University Hospital, Philadelphia, Pennsylvania, USA.
authors.forename: L H
authors.initials: LH
authors.lastname: Leopold
authors.forename: S K
authors.initials: SK
authors.lastname: Shore
authors.forename: E P
authors.initials: EP
authors.lastname: Reddy
mesh_terms: D000818:Animals; D001483:Base Sequence; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D015316:Genetic Therapy; D006801:Humans; D007700:Kinetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D008969:Molecular Sequence Data; D016337:RNA, Catalytic / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D013379:Substrate Specificity; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D016337:RNA, Catalytic; D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl