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• W1903991639 abstract "Monocytes are important target cells for anti-inflammatory antisense strategies. However, monocytes are characterized by strong phagocytic and catalytic activity which may limit the effect of antisense oligonucleotides. Intracellular distribution of oligonucleotides in monocytes and the effect of cationic lipids on oligonucleotide uptake in monocytes and other leukocytes have not been evaluated. We investigated cationic lipid-mediated uptake of oligonucleotides in human monocytes and lymphocyte subpopulations. Incorporation of oligonucleotides was quantified by flow cytometry and by confocal microscopy. In the absence of cationic lipids, nearly 100% of monocytes and of B lymphocytes incorporated oligonucleotides compared with only 12% of natural killer cells and 1% of T lymphocytes. The amount of oligonucleotide uptake per cell, as determined by mean fluoresence intensity of positive cells, was four times higher in monocytes than in B lymphocytes. Cationic lipids, which form complexes with oligonucleotides, markedly enhanced the amount of oligonucleotide uptake in all cell types and were most effective at a ratio of 1.1 of positive-to-negative molar charges. In monocytes, oligonucleotides incorporated spontaneously (without a lipid carrier) were trapped in cytoplasmic vesicles. In contrast, cationic lipid-mediated uptake of fluorescence-labeled oligonucleotides resulted in cytoplasmic and nuclear staining. We conclude that 1) monocyte and lymphocyte subpopulations differ in the degree of spontaneous oligonucleotide uptake, and 2) lipofectin both quantitatively and qualitatively affects this uptake. Our results may explain the necessary role of cationic lipids in most antisense models with leukocytes as target cells." @default.
• W1903991639 created "2016-06-24" @default.
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• W1903991639 date "1998-05-01" @default.
• W1903991639 modified "2023-09-27" @default.
• W1903991639 title "Spontaneous and cationic lipid-mediated uptake of antisense oligonucleotides in human monocytes and lymphocytes." @default.
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