Correlation of activity with stability of chemically modified ribozymes in nuclei suspension. NLM AIDSLINE Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

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Correlation of activity with stability of chemically modified ribozymes in nuclei suspension.

Antisense Nucleic Acid Drug Dev. 1996 Summer;6(2):111-8. Unique Identifier : AIDSLINE MED/97000183
Heidenreich O; Xu X; Swiderski P; Rossi JJ; Nerenberg M; Scripps Research Institute, Department of Molecular and; Experimental Medicine, La Jolla, CA 92037, USA.

Abstract: 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.
Keywords: Animal Cell Line, Transformed Cell Nucleus/*METABOLISM Cell Transformation, Viral Fibroblasts/METABOLISM/PATHOLOGY Gene Products, tax/*GENETICS/METABOLISM HTLV-I Mice Mice, Transgenic RNA, Catalytic/GENETICS/*METABOLISM RNA, Viral/GENETICS/*METABOLISM Structure-Activity Relationship Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. JOURNAL ARTICLEKWDanimalcellline,transformedcellnucleus/KWDmetabolismcelltransformation,viralfibroblasts/metabolism/pathologygeneproducts,tax/KWDgenetics/metabolismhtlv-imicemice,transgenicrna,catalytic/genetics/KWDmetabolismrna,viral/genetics/KWDmetabolismstructure-activityrelationshipsupport,non-uKWDsKWDgov'tsupport,uKWDsKWDgov't,pKWDhKWDsKWDjournalarticle
970228
M9721909

Copyright © 1997 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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