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- W2317778488 abstract "Catalytic RNA or ribozymes have important potential applications as molecular biological tools in the study of gene expression and as therapeutic inhibitors of disease-causing genes. Very little is known, however, about the cellular uptake mechanisms of exogenously delivered synthetic ribozymes. In this study, we have characterized the uptake properties of a synthetic, 2'-O-methyl-modified ribozyme containing U4/U7 amino groups within the catalytic core of the hammerhead motif. The cellular uptake of the internally [32P]-radiolabeled hammerhead ribozyme in U87-MG glioma cells was temperature, energy, and pH dependent and involved an active process that could be competed with cold ribozyme of the same chemistry and sequence, an all 2'-O-methyl-modified ribozyme of the same sequence, antisense PS-ODNs, and a variety of other polyanions (salmon sperm DNA, spermidine, dextran sulfate, and heparin). Subcellular distribution studies of fluorescently labeled ribozymes confirmed an extranuclear, punctate localization similar to that observed for an endosomal marker, dextran. Our study highlights that hammerhead ribozymes, despite exhibiting a defined secondary structure, enter cells by an endocytic mechanism that appears to be similar to that reported for a variety of antisense ODNs. These observations should facilitate the development of more efficient delivery systems." @default.
- W2317778488 created "2016-06-24" @default.
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- W2317778488 date "1997-08-01" @default.
- W2317778488 modified "2023-09-27" @default.
- W2317778488 title "Cellular Uptake Properties of a 2‵-Amino/2‵-O-Methyl-Modified Chimeric Hammerhead Ribozyme Targeted to the Epidermal Growth Factor Receptor mRNA" @default.
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- W2317778488 doi "https://doi.org/10.1089/oli.1.1997.7.319" @default.
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