A SERUM-RESISTANT CYTOFECTIN FOR CELLULAR DELIVERY OF ANTISENSE OLIGODEOXYNUCLEOTIDES AND PLASMID DNA

Development of antisense technology has focused in part on creating im proved methods for delivering oligodeoxynucleotides (ODNs) to cells, I n this report, we describe a cationic lipid that, when formulated with the fusogenic lipid dioleoylphosphatidylethanolamine, greatly improve s the cellular uptake properties of antisense ODNs, as well as plasmid DNA, This lipid formulation, termed GS 2888 cytofectin, (i) efficient ly transfects ODNs and plasmids into many cell types in the presence o r 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 L ipofectin liposome, and (iii) is greater than or equal to 20-fold more effective at eliciting antisense effects in the presence of serum whe n compared to Lipofectin, Here we show antisense effects using GS 2888 cytofectin together with C-5 propynyl pyrimidine phosphorethioate ODN s in which we achieve inhibition of gene expression using low nanomola r concentrations of ODN, This agent expands the utility of antisense O DNs for their use in understanding gene function and offers the potent ial for its use in DNA delivery applications in vivo.