Development of antibody-siRNA conjugate targeted to cardiac and skeletal muscles

被引：150

作者：

Sugo, Tsukasa ^{[1
]}

Terada, Michiko ^{[1
]}

Oikawa, Tatsuo ^{[2
]}

Miyata, Kenichi ^{[1
]}

Nishimura, Satoshi ^{[2
]}

Kenjo, Eriya ^{[1
]}

Ogasawara-Shimizu, Mari ^{[1
]}

Makita, Yukimasa ^{[1
]}

Imaichi, Sachiko ^{[1
]}

Murata, Shumpei ^{[1
]}

Otake, Kentaro ^{[1
]}

Kikuchi, Kuniko ^{[1
]}

Teratani, Mika ^{[1
]}

Masuda, Yasushi ^{[1
]}

Kamei, Takayuki ^{[1
]}

Takagahara, Shuichi ^{[2
]}

Ikeda, Shota ^{[2
]}

Ohtaki, Tetsuya ^{[1
]}

Matsumoto, Hirokazu ^{[1
]}

机构：

[1] Takeda Pharmaceut Co Ltd, Div Pharmaceut Res, Integrated Technol Res Labs, 26-1 Muraoka Higashi 2-Chome, Fujisawa, Kanagawa 2518555, Japan

[2] Takeda Pharmaceut Co Ltd, Div Pharmaceut Res, Cardiovasc & Metab Drug Discovery Unit, 26-1 Muraoka Higashi 2-Chome, Fujisawa, Kanagawa 2518555, Japan

来源：

JOURNAL OF CONTROLLED RELEASE | 2016年 / 237卷

关键词：

Skeletal muscle; Heart; CD71; Transferrin; siRNA; Conjugate; Myostatin; Peripheral artery disease (PAD); Drug delivery system; Targeting; Antibody; Intramuscular injection; PERIPHERAL ARTERIAL-DISEASE; SMALL INTERFERING RNAS; BLOOD-BRAIN-BARRIER; TRANSFERRIN RECEPTOR; IN-VIVO; MONOCLONAL-ANTIBODY; CELL-PROLIFERATION; HEART-FAILURE; DNA UPTAKE; MYOSTATIN;

D O I：

10.1016/j.jconrel.2016.06.036

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Despite considerable efforts to develop efficient carriers, the major target organ of short-interfering RNAs (siRNAs) remains limited to the liver. Expanding the application outside the liver is required to increase the value of siRNAs. Here we report on a novel platform targeted to muscular organs by conjugation of siRNAs with anti-CD71 Fab' fragment. This conjugate showed durable gene-silencing in the heart and skeletal muscle for one month after intravenous administration in normal mice. In particular, 1 mu g siRNA conjugate showed significant gene-silencing in the gastrocnemius when injected intramuscularly. In a mouse model of peripheral artery disease, the treatment with myostatin-targeting siRNA conjugate by intramuscular injection resulted in significant silencing of myostatin and hypertrophy of the gastrocnemius, which was translated into the recovery of running performance. These data demonstrate the utility of antibody conjugation for siRNA delivery and the therapeutic potential for muscular diseases. (C) 2016 Elsevier B.V. All rights reserved.

引用

页码：1 / 13

页数：13

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