Novel Types of Small RNA Exhibit Sequence- and Target-dependent Angiogenesis Suppression Without Activation of Toll-like Receptor 3 in an Age-related Macular Degeneration (AMD) Mouse Model.
RNA interference (RNAi) has become a powerful tool for suppressing gene expression in vitro and in vivo. A great deal of evidence has demonstrated the potential for the use of synthetic small interfering RNAs (siRNAs) as therapeutic agents. However, the application of siRNA to clinical medicine is still limited, mainly due to sequence-independent suppression of angiogenesis mediated by Toll-like receptor 3 (TLR3). Here, we describe novel types of synthetic RNA, named nkRNA and PnkRNA, that exhibit sequence-specific gene silencing through RNAi without activating TLRs or RIG-I-like receptor signaling. In addition, we confirmed the therapeutic effect for the novel types of RNA in an animal model of age-related macular degeneration (AMD) without retinal degeneration. These data indicate that nkRNA and PnkRNA are of great potential utility as therapies against blinding choroidal neovascularization due to AMD.
Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan.
Masakatsu
M
Takanashi
Animal Research Center, Tokyo Medical University, Tokyo, Japan.
Katsuko
K
Sudo
Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan.
Shinobu
S
Ueda
Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan.
Shin-Ichiro
S
Ohno
Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan.
Yuko
Y
Yamada
Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan.
Yasuhiro
Y
Osakabe
Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan.
Hiroshi
H
Goto
Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan.
Yoshimichi
Y
Matsunaga
Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan.
Akio
A
Ishikawa
Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan.
Yoshihiko
Y
Usui
Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan.
Masahiko
M
Kuroda