title: The biological effect of an antisense oligonucleotide depends on its route of endocytosis and trafficking.
abstract: We demonstrate that the biological effect of an oligonucleotide is influenced by its route of cellular uptake. Utilizing a splice-switching antisense oligonucleotide (SSO) and a sensitive reporter assay involving correction of RNA splicing, we examined induction of luciferase in cells treated either with various concentrations of an unconjugated ("free") SSO or an SSO conjugated to a bivalent RGD ligand that promotes binding to the alphavbeta3 integrin (RGD-SSO). Under conditions of equal accumulation in cells, the RGD-SSO consistently had a greater effect on luciferase induction than the unconjugated SSO. We determined that the RGD-SSO and the unconjugated SSO were internalized by distinct endocytotic pathways, suggesting that the route of internalization affects the magnitude of the biological response.
authors.affiliation: Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Md Rowshon
authors.initials: MR
authors.lastname: Alam
authors.forename: Xin
authors.initials: X
authors.lastname: Ming
authors.forename: Vidula
authors.initials: V
authors.lastname: Dixit
authors.forename: Michael
authors.initials: M
authors.lastname: Fisher
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.forename: Rudolph L
authors.initials: RL
authors.lastname: Juliano
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D002460:Cell Line; D004705:Endocytosis; D005470:Fluorometry; D006801:Humans; D018613:Microscopy, Confocal; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012326:RNA Splicing
chemical_list: D000199:Actins; D016376:Oligonucleotides, Antisense