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      A serum-resistant cytofectin for cellular delivery of antisense oligodeoxynucleotides and plasmid DNA.

      Proceedings of the National Academy of Sciences of the United States of America
      Base Sequence, Cations, Cell Line, Cell Membrane Permeability, Culture Media, Drug Carriers, Fluoresceins, HeLa Cells, Humans, In Vitro Techniques, Lipids, chemistry, Molecular Sequence Data, Oligonucleotides, Antisense, administration & dosage, genetics, Phosphatidylethanolamines, Plasmids, Transfection

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          Development of antisense technology has focused in part on creating improved methods for delivering oligodeoxynucleotides (ODNs) to cells. In this report, we describe a cationic lipid that, when formulated with the fusogenic lipid dioleoylphosphatidyliethanolamine, greatly improves the cellular uptake properties of antisense ODNs, as well as plasmid DNA. This lipid formulation, termed GS 2888 cytofectin, (i) efficiently transfects ODNs and plasmids into many cell types in the presence or absence of 10% serum in the medium, (ii) uses a 4- to 10-fold lower concentration of the agent as compared to the commercially available Lipofectin liposome, and (iii) is > or = 20-fold more effective at eliciting antisense effects in the presence of serum when compared to Lipofectin. Here we show antisense effects using GS 2888 cytofectin together with C-5 propynyl pyrimidine phosphorothioate ODNs in which we achieve inhibition of gene expression using low nanomolar concentrations of ODN. This agent expands the utility of antisense ODNs for their use in understanding gene function and offers the potential for its use in DNA delivery applications in vivo.

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