Silencing of BCR/ABL Chimeric Gene in Human Chronic Myelogenous Leukemia Cell Line K562 by siRNA-Nuclear Export Signal Peptide Conjugates

Yasuhiro Shinkai, Shinichi Kashihara, Go Minematsu, Hirofumi Fujii, Madoka Naemura, Yojiro Kotake, Yasutaka Morita, Koichiro Ohnuki, Alesya A. Fokina, Dmitry A. Stetsenko, Vyacheslav V. Filichev, Masayuki Fujii

Результат исследования: Научные публикации в периодических изданияхстатьярецензирование

4 Цитирования (Scopus)

Аннотация

Herein we described the synthesis of siRNA-NES (nuclear export signal) peptide conjugates by solid phase fragment coupling and the application of them to silencing of bcr/abl chimeric gene in human chronic myelogenous leukemia cell line K562. Two types of siRNA-NES conjugates were prepared, and both sense strands at 5′ ends were covalently linked to a NES peptide derived from TFIIIA and HIV-1 REV, respectively. Significant enhancement of silencing efficiency was observed for both of them. siRNA-TFIIIA NES conjugate suppressed the expression of BCR/ABL gene to 8.3% at 200 nM and 11.6% at 50 nM, and siRNA-HIV-1REV NES conjugate suppressed to 4.0% at 200 nM and 6.3% at 50 nM, whereas native siRNA suppressed to 36.3% at 200 nM and 30.2% at 50 nM. We could also show complex of siRNA-NES conjugate and designed amphiphilic peptide peptideβ7 could be taken up into cells with no cytotoxicity and showed excellent silencing efficiency. We believe that the complex siRNA-NES conjugate and peptideβ7 is a promising candidate for in vivo use and therapeutic applications.

Язык оригиналаанглийский
Страницы (с-по)168-175
Число страниц8
ЖурналNucleic Acid Therapeutics
Том27
Номер выпуска3
DOI
СостояниеОпубликовано - июн 2017

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