SPECIFIC TARGETING OF ANTISENSE OLIGONUCLEOTIDES TO NEUTROPHILS

The ability of three different hydrophobic ligands (cholic acid, chole sterol, and the tetrapeptide fMLFY) to increase the uptake of an antis ense (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 t he uptake of anti-actin oligomer. When fMLFY is the ligand, the cellul ar uptake is much less than that of anti-actin oligomer alone, but the biological consequences are much more significant. Our results are co nsistent with the hypothesis that the fMLFY conjugate of the anti-acti n oligomer is internalized via a different route, and reaches its targ et site most efficiently.