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Involvement of an intracellular vesicular transport process in naked-sgRNA-mediated TRUE gene silencing.

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Title: Involvement of an intracellular vesicular transport process in naked-sgRNA-mediated TRUE gene silencing.
Authors: Tamura, Masato Browse this author →KAKEN DB
Kawano, Mitsuoki Browse this author →KAKEN DB
Sato, Mari Browse this author →KAKEN DB
Nashimoto, Masayuki Browse this author →KAKEN DB
Keywords: TRUE gene silencing
small guide RNA
vesicular transport
Issue Date: Oct-2015
Publisher: Spandidos Publications
Journal Title: Molecular medicine reports
Volume: 12
Issue: 4
Start Page: 6365
End Page: 6369
Publisher DOI: 10.3892/mmr.2015.4160
PMID: 26238202
Abstract: tRNase ZL-utilizing efficacious gene silencing (TRUE gene silencing) is an RNA-mediated gene expression control technology with therapeutic potential. Recently, our group demonstrated that a heptamer, mh1 (Bcl‑2), targeting human Bcl-2 mRNA, can be taken up by cells without the use of any transfection reagents and can induce the apoptosis of leukemia cells. However, little is known regarding the mechanism of naked small guide (sg)RNA uptake by cultured cells. Therefore, in the present study the effects of various inhibitors on the induction of apoptosis by naked sgRNA treatment were investigated in order to identify the uptake pathway required for sgRNA function in cultured cells. Addition of the endocytosis inhibitors chlorpromazine, nystatin or methyl‑β‑cyclodextrin together with naked effective sgRNA was unable to diminish the apoptosis‑inducing effects of naked sgRNA or the reduction in target mRNA, suggesting that functional uptake of sgRNA by cells is clathrin‑, caveolae‑ and raft‑independent. Next, chloroquine, an inhibitor of lysosome acidification, and brefeldin A, an inhibitor that blocks protein transport from the Golgi apparatus to the endoplasmic reticulum were administered. In the presence of these compounds, the apoptosis‑inducing effects of naked sgRNA were reduced. These results suggest that a vesicular transport process is involved in sgRNA‑mediated TRUE gene silencing. A greater understanding of how naked sgRNAs enter cells and how they reach their target RNAs may aid in the design of more specifically‑targeted and potent sgRNA drugs.
Type: article
Appears in Collections:歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 田村 正人

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