The Biological Effect of an Antisense Oligonucleotide Depends on Its Route of Endocytosis and Trafficking

Overview

Journal Oligonucleotides

Specialties Biochemistry
Molecular Biology

Date 2009 Dec 30

PMID 20038250

Citations 41

Authors

Md Rowshon Alam

Xin Ming

Vidula Dixit

Michael Fisher

Xiaoyuan Chen

Rudolph L Juliano

Affiliations

Soon will be listed here.

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.

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