Biological activity of oligonucleotide-poly(L-lysine) conjugates: mechanism of cell uptake.
We have previously shown that antisense oligomers linked to poly(L-lysine) (PLL) exhibit antiviral properties against vesicular stomatitis virus (VSV) at concentrations lower than 1 microM. The conjugation to PLL provides an interesting alternative to natural or neutral oligomers to increase the biological effects of antisense oligomers. The internalization pathway of oligomer-PLL conjugates as compared to unconjugated oligomers has been studied in L929 cells. In parallel to their enhanced antiviral activity, PLL increases greatly the uptake of fluorescently tagged oligomers. This internalization follows a classical endocytic pathway and the oligomer has to be cleaved from PLL in the cell to exhibit an antiviral effect.
Leonetti
J P
JP
Laboratoire de Biochimie des Protéines, CNRS UA 1191, Université des Sciences et Techniques du Languedoc, Montpellier, France.
Degols
G
G
Lebleu
B
B
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis*; D001483:Base Sequence; D001692:Biological Transport; D002213:Capsid / Q000235:genetics; D007700:Kinetics; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis*; D011107:Polylysine; D012333:RNA, Messenger / Q000235:genetics; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D014758:Viral Core Proteins / Q000235:genetics
D000998:Antiviral Agents; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D014758:Viral Core Proteins; D011107:Polylysine