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

被引：48

作者：

Alam, Md. Rowshon ^{[1
]}

Ming, Xin ^{[1
]}

Dixit, Vidula ^{[1
]}

Fisher, Michael ^{[1
]}

Chen, Xiaoyuan ^{[2
]}

Juliano, Rudolph L. ^{[1
]}

机构：

[1] Univ N Carolina, Eshelman Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC 27599 USA

[2] Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA

来源：

OLIGONUCLEOTIDES | 2010年 / 20卷 / 02期

关键词：

CLATHRIN-INDEPENDENT ENDOCYTOSIS; CELL-PENETRATING PEPTIDES; INTRACELLULAR DELIVERY; MEDIATED ENDOCYTOSIS; RNA-INTERFERENCE; SIRNA DELIVERY; NUCLEIC-ACIDS; PATHWAYS; CAVEOLAE; NANOPARTICLES;

D O I：

10.1089/oli.2009.0211

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 alpha v beta 3 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.

引用

页码：103 / 109

页数：7

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