title: Intracellular ribozyme applications.
abstract: The exquisite target selectivity of trans -acting ribozymes has fostered their use as potential therapeutic agents and tools for down-regulating cellular transcripts. In living cells, free diffusion of RNAs is extremely limited, if it exists at all. Thus, getting ribozymes to base-pair with their cognate targets requires co-localizing the ribozyme transcript with the target RNA. In addition, not all sites along a given target RNA are equally accessible to ribozyme base pairing. Cellular proteins greatly influence the trafficking and structure of RNA, and therefore making ribozymes work effectively in cells a significant challenge. This article addresses the problems of getting engineered ribozymes to effectively pair with and cleave targets in cells. The work described here illuminates methods for target-site selection on native mRNAs, methods for ribozyme expression, and strategies for obtaining a discrete intracellular localization of ribozymes.
authors.affiliation: Division of Molecular Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010-3011, USA.
authors.forename: D
authors.initials: D
authors.lastname: Castanotto
authors.forename: J R
authors.initials: JR
authors.lastname: Li
authors.forename: A
authors.initials: A
authors.lastname: Michienzi
authors.forename: M-A
authors.initials: MA
authors.lastname: Langlois
authors.forename: N S
authors.initials: NS
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Puymirat
authors.forename: J J
authors.initials: JJ
authors.lastname: Rossi
mesh_terms: D015152:Blotting, Northern; D002455:Cell Division; D015536:Down-Regulation; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D009223:Myotonic Dystrophy / Q000378:metabolism; D009687:Nuclear Proteins; D009690:Nucleic Acid Conformation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D016337:RNA, Catalytic / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
chemical_list: D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016337:RNA, Catalytic; D012333:RNA, Messenger; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2