Delivery of small interfering RNA with a synthetic collagen poly(Pro-Hyp-Gly) for gene silencing in vitro and in vivo.
Silencing gene expression by small interfering RNAs (siRNAs) has become a powerful tool for the genetic analysis of many animals. However, the rapid degradation of siRNA and the limited duration of its action in vivo have called for an efficient delivery technology. Here, we describe that siRNA complexed with a synthetic collagen poly(Pro-Hyp-Gly) (SYCOL) is resistant to nucleases and is efficiently transferred into cells in vitro and in vivo, thereby allowing long-term gene silencing in vivo. We found that the SYCOL-mediated local application of siRNA targeting myostatin, coding a negative regulator of skeletal muscle growth, in mouse skeletal muscles, caused a marked increase in the muscle mass within a few weeks after application. Furthermore, in vivo administration of an anti-luciferase siRNA/SYCOL complex partially reduced luciferase expression in xenografted tumors in vivo. These results indicate a SYCOL-based non-viral delivery method could be a reliable simple approach to knockdown gene expression by RNAi in vivo as well as in vitro.
Adachi
Taro
T
Department of Life Systems, Institute of Technology and Science, The University of Tokushima Graduate School, 2-1 Minami-Jyosanjima, Japan.
Kawakami
Emi
E
Ishimaru
Naozumi
N
Ochiya
Takahiro
T
Hayashi
Yoshio
Y
Ohuchi
Hideyo
H
Tanihara
Masao
M
Tanaka
Eiji
E
Noji
Sumihare
S
D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D003094:Collagen / Q000737:chemistry*; D017931:DNA Primers; D020868:Gene Silencing; D066298:In Vitro Techniques; D051379:Mice; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D034741:RNA, Small Interfering; D003094:Collagen