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In Vivo RNAi Efficacy of Palmitic Acid‐Conjugated Dicer‐Substrate siRNA in a Subcutaneous Tumor Mouse Model
Author(s) -
Kubo Takanori,
Yanagihara Kazuyoshi,
Seyama Toshio
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12720
Subject(s) - rna interference , dicer , small interfering rna , gene silencing , rna , rna silencing , microbiology and biotechnology , biology , green fluorescent protein , in vivo , transfection , chemistry , gene , biochemistry , genetics
Short interfering RNAs are used in RNA interference technology and are powerful tools for target gene silencing in a sequence‐specific manner. In this study, we synthesized Dicer‐substrate siRNAs consisting of 27‐nt double‐stranded RNAs conjugated with palmitic acid at the 5′‐end of the sense strand and investigated their RNA interference efficacies in vitro and in vivo . The palmitic acid‐conjugated 27‐nt DsiRNAs (C16‐Dsi27RNAs) were prepared by our simple synthesis strategy and achieved a good yield. C16‐Dsi27RNAs showed enhanced in vitro RNA interference potency compared with not only non‐modified Dsi27RNAs but also cholesterol‐conjugated Dsi27RNAs against both an exogenous enhanced green fluorescent protein and the endogenous vascular endothelial growth factor gene in a human scirrhous‐type gastric cancer cell line that stably expressed the enhanced green fluorescent protein gene (GCIY‐eGFP). Additionally, C16‐Dsi27RNAs had potent gene silencing activity against both enhanced green fluorescent protein and vascular endothelial growth factor as target genes in a subcutaneous tumor mouse model generated from GCIY‐eGFP cells administered by intratumoral injection. These results suggest that the C16‐Dsi27RNAs will be useful next‐generation RNA interference molecules that can overcome the problems associated with RNA interference technology.