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This article will examine recent developments concerning the cellular uptake and subcellular trafficking of antisense oligonucleotides. It will also examine the merits of various delivery strategies for oligonucleotides. The use of conjugates of oligonucleotides with 'cell penetrating peptides' as a promising delivery technology will be emphasized.
PAMAM dendrimers are cationic polymers that have been used for the delivery of genes and oligonucleotides to cells. However, little is known about the behavior of dendrimer-nucleic acid complexes once they reach the cell interior. To pursue this issue, we prepared dendrimers conjugated with the fluorescent dye Oregon green 488. These were used in(More)
This review critically examines current understanding of the kinetics and biodistribution of antisense oligonucleotides, both at the cellular level and at the level of the intact organism. The pharmacodynamic relationships between biodistribution and the ultimate biological effects of antisense agents are considered. The problems and advantages inherent in(More)
PURPOSE To investigate the potential use of PAMAM dendrimers for the delivery of antisense oligonucleotides into cells under conditions that mimic the in vivo environment. METHODS We used HeLa cells stably transfected with plasmid pLuc/705 which has a luciferase gene interrupted by a human beta-globin intron mutated at nucleotide 705, thus causing(More)
A variety of techniques are currently available to enhance the cellular uptake and pharmacological effectiveness of antisense oligonucleotides in the in vitro setting. The choice of technique will depend on the context of investigation, the likelihood of cytotoxity due to the delivery agents, and the ease and convenience of the approach. The considerations(More)
There has been great interest recently in therapeutic use of nucleic acids including genes, ribozymes and antisense oligonucleotides. Despite recent improvements in delivering antisense oligonucleotides to cells in culture, nucleic acid-based therapy is still often limited by the poor penetration of the nucleic acid into the cytoplasm and nucleus of cells.(More)
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