Oligonucleotide enhanced XXXX of @entity8779 for @entity706 cells.

@entity137 @entity706 @entity4349 @entity8779 @entity876 @entity1583
Oligonucleotides offer the potential to manipulate gene expression in targeted cells which might be exploitable for therapeutic benefit. The effects of combining a phosphorothioate oligonucleotide OL(1) @entity876 , which transiently down-regulates @entity876 levels, with an @entity4349 , @entity8779 , on the growth of wild-type @entity876 WMN gene-expressing @entity706 cells was evaluated. Fluorescent OL(1) @entity876 , was used to demonstrate oligonucleotide uptake and retention by the WMN cells. Uptake was maximal at 24 hours and compared to baseline (0 hours) increasing apoptotic cells were evident in WMN cells treated with OL(1) (1 microM) alone and in combination with @entity8779 (0.2 nM) for 24 to 48 hours. In cells treated with OL(1) @entity876 and @entity8779 , truncated @entity876 message of a predicted 201 base pair length based on RNAase H cleavage of the OL(1) @entity876 - @entity876 mRNA heteroduplex was detected after 7 hours of incubation. The message for @entity876 was transiently downregulated as detected by RT-PCR analysis at 24 hours, and protein levels transiently reduced at 36 hours, as shown by a quantitative Western blot. Corresponding to these events, the growth of WMN cells ceased after 48 hours in the concurrent presence of OL(1) @entity876 and @entity8779 and, the @entity706 cells were dead after 72 hours. No reduction in @entity1583 colony forming cell capacity of similarly treated @entity1583 progenitor cells harvested from cytokine-mobilized blood by apheresis was observed. Therefore, synergistic @entity137 of @entity8779 for @entity706 cells treated with an oligonucleotide targeting @entity876 message was demonstrated at oligonucleotide and @entity8779 concentrations which were minimally toxic to @entity1583 progenitor cells. This approach offers new opportunities for purging of @entity706 cells from @entity1583 harvests and @entity706 therapy.
