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Lookup NU author(s): Professor Olaf Heidenreich
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To examine hammerhead ribozyme activity in the nuclear environment, we have used nuclei isolated from HTLV-I tax transformed fibroblasts to evaluate ribozymes targeted against HTLV-I tax RNA. The ribozyme activity in nuclei suspension was strongly dependent on the resistance of the particular ribozyme to endogenous nucleases. A ribozyme containing exclusively 2'-deoxynucleotides in its stems cleaved target RNA by its catalytic activity in the absence of proteins and caused degradation in their presence by induction of nuclear RNase H activity. A ribozyme containing 2'-amino- and 2'-fluoropyrimidine nucleosides in combination with terminal phosphorothioate linkages was significantly more stable in nuclei suspension and also exhibited a more than threefold higher cleavage efficacy than its unmodified counterpart. The increased resistance against nuclease degradation is mainly due to terminal phosphorothioate linkages, suggesting that both 5' and 3'-exonucleases are primarily responsible for the nuclear degradation of oligonucleotides.
Author(s): Heidenreich O, Xu X, Swiderski P, Rossi JJ, Nerenberg M
Publication type: Article
Publication status: Published
Journal: Antisense and Nucleic Acid Drug Development
Year: 1996
Volume: 6
Issue: 2
Pages: 111-118
ISSN (print): 1545-4576
ISSN (electronic): 1557-8526
