Specific targeting of antisense oligonucleotides to neutrophils.
The ability of three different hydrophobic ligands (cholic acid, cholesterol, and the tetrapeptide fMLFY) to increase the uptake of an antisense (anti-actin) oligomer into neutrophils was analyzed. In agreement with the literature (Boutorin et al., 1989; Letsinger et al., 1989), we found that cholic acid and cholesterol conjugates greatly enhance the uptake of anti-actin oligomer. When fMLFY is the ligand, the cellular uptake is much less than that of anti-actin oligomer alone, but the biological consequences are much more significant. Our results are consistent with the hypothesis that the fMLFY conjugate of the anti-actin oligomer is internalized via a different route, and reaches its target site most efficiently.
Chow
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Department of Oncology, McGill University, Montreal General Hospital. Quebec, Canada.
Juby
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Brousseau
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D000199:Actins / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D002784:Cholesterol / Q000494:pharmacology*; D019826:Cholic Acid; D002793:Cholic Acids / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*
D000199:Actins; D002793:Cholic Acids; C090572:N-formylmethionyl-leucyl-phenylalanyl-tyrosine; D016376:Oligonucleotides, Antisense; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002784:Cholesterol; D019826:Cholic Acid