RRC ID |
71763
|
Author |
Machitani M, Sakurai F, Wakabayashi K, Tachibana M, Fujiwara T, Mizuguchi H.
|
Title |
Enhanced Oncolytic Activities of the Telomerase-Specific Replication-Competent Adenovirus Expressing Short-Hairpin RNA against Dicer.
|
Journal |
Mol Cancer Ther
|
Abstract |
Oncolytic viruses have been receiving much attention as potential agents for cancer treatment. Among the various types of oncolytic viruses, the telomerase-specific replication-competent adenovirus (TRAD), which carries the tumor-specific promoter-driven E1 gene expression cassette, exhibits efficient antitumor effects. The development of a novel TRAD that shows higher replication efficiency and antitumor activity would be highly beneficial for safer and more efficient cancer therapy. We recently demonstrated that the endoribonuclease Dicer significantly inhibits the replication of wild-type adenovirus (Ad) via the processing of viral-associated (VA)-RNAs, which are Ad-encoded small noncoding RNAs, and that the knockdown of Dicer leads to enhanced VA-RNA expression and Ad replication after infection with wild-type Ad. Based on these findings, we herein developed a novel TRAD expressing short-hairpin RNA against Dicer (shDicer; TRAD-shDicer). After infection, TRAD-shDicer efficiently induced the knockdown of Dicer. TRAD-shDicer showed significantly higher replication efficiency and tumor cell lysis activity compared with the conventional TRAD in tumor cells. The Dicer expression levels and viabilities of normal cells were not altered by infection with TRAD-shDicer. These results indicate that TRAD-shDicer is a potent antitumor reagent by virtue of its enhanced oncolytic activity. Mol Cancer Ther; 16(1); 251-9. ©2016 AACR.
|
Volume |
16(1)
|
Pages |
251-259
|
Published |
2017-1-1
|
DOI |
10.1158/1535-7163.MCT-16-0383
|
PII |
1535-7163.MCT-16-0383
|
PMID |
27760834
|
MeSH |
Adenoviridae / genetics*
Animals
Cell Line, Tumor
Disease Models, Animal
Female
Gene Expression*
Gene Knockdown Techniques
Gene Order
Genetic Therapy / methods
Genetic Vectors / genetics*
Humans
Mice
Oncolytic Virotherapy / methods
Oncolytic Viruses / genetics*
Organ Specificity / genetics
RNA, Small Interfering / genetics*
Ribonuclease III / genetics*
Telomerase / genetics
Telomerase / metabolism*
Transduction, Genetic
Tumor Burden / genetics
Virus Replication*
Xenograft Model Antitumor Assays
|
IF |
5.615
|
Resource |
Human and Animal Cells |
HeLa(RCB0007) |