Work

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

Year: 2009

Type: article

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.

Source: Oligonucleotides

DOI: 10.1089/oli.2009.0211

Authors: Md. Rowshon Alam, Xin Ming, Vidula Dixit, Michael Fisher, Xiaoyuan Chen, Rudolph L. Juliano

Institutions: University of North Carolina at Chapel Hill, Stanford Medicine, Stanford University

Language: English

Topic: RNA Interference and Gene Delivery

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences