Oligopeptide complex for targeted non-viral gene delivery to adipocytes

Young Wook Won; Partho Protim Adhikary; Kwang Suk Lim; Hyung Jin Kim; Jang Kyoung Kim; Yong Hee Kim

doi:10.1038/nmat4092

Oligopeptide complex for targeted non-viral gene delivery to adipocytes

Young Wook Won, Partho Protim Adhikary, Kwang Suk Lim, Hyung Jin Kim, Jang Kyoung Kim, Yong Hee Kim

Research output: Contribution to journal › Article › peer-review

119 Scopus citations

Abstract

Commercial anti-obesity drugs acting in the gastrointestinal tract or the central nervous system have been shown to have limited efficacy and severe side effects. Anti-obesity drug development is thus focusing on targeting adipocytes that store excess fat. Here, we show that an adipocyte-targeting fusion-oligopeptide gene carrier consisting of an adipocyte-targeting sequence and 9-arginine (ATS-9R) selectively transfects mature adipocytes by binding to prohibitin. Injection of ATS-9R into obese mice confirmed specific binding of ATS-9R to fat vasculature, internalization and gene expression in adipocytes. We also constructed a short-hairpin RNA (shRNA) for silencing fatty-acid-binding protein 4 (shFABP4), a key lipid chaperone in fatty-acid uptake and lipid storage in adipocytes. Treatment of obese mice with ATS-9R/shFABP4 led to metabolic recovery and body-weight reduction (>20%). The ATS-9R/shFABP4 oligopeptide complex could prove to be a safe therapeutic approach to regress and treat obesity as well as obesity-induced metabolic syndromes.

Original language	English (US)
Pages (from-to)	1157-1164
Number of pages	8
Journal	Nature materials
Volume	13
Issue number	12
DOIs	https://doi.org/10.1038/nmat4092
State	Published - Dec 1 2014
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Materials Science
Condensed Matter Physics
Mechanics of Materials
Mechanical Engineering

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title = "Oligopeptide complex for targeted non-viral gene delivery to adipocytes",

abstract = "Commercial anti-obesity drugs acting in the gastrointestinal tract or the central nervous system have been shown to have limited efficacy and severe side effects. Anti-obesity drug development is thus focusing on targeting adipocytes that store excess fat. Here, we show that an adipocyte-targeting fusion-oligopeptide gene carrier consisting of an adipocyte-targeting sequence and 9-arginine (ATS-9R) selectively transfects mature adipocytes by binding to prohibitin. Injection of ATS-9R into obese mice confirmed specific binding of ATS-9R to fat vasculature, internalization and gene expression in adipocytes. We also constructed a short-hairpin RNA (shRNA) for silencing fatty-acid-binding protein 4 (shFABP4), a key lipid chaperone in fatty-acid uptake and lipid storage in adipocytes. Treatment of obese mice with ATS-9R/shFABP4 led to metabolic recovery and body-weight reduction (>20\%). The ATS-9R/shFABP4 oligopeptide complex could prove to be a safe therapeutic approach to regress and treat obesity as well as obesity-induced metabolic syndromes.",

author = "Won, \{Young Wook\} and Adhikary, \{Partho Protim\} and Lim, \{Kwang Suk\} and Kim, \{Hyung Jin\} and Kim, \{Jang Kyoung\} and Kim, \{Yong Hee\}",

note = "Funding Information: This work was partially supported by grants from the National Research Foundation of Korea (2013030789), the Brain Korea 21 plus program (22A20130011095), and the Korean Health Technology R\&D project through the Ministry of Health \& Welfare (HI13C-1938-010013). All the confocal microscopy and Cellvizio imaging experiments were carried out at Korea Basic Science Institute, Chuncheon Center, Chuncheon-city, Korea. We are sincerely grateful for their assistance in performing experiments and data analysis. Publisher Copyright: {\textcopyright} 2014 Macmillan Publishers Limited. All rights reserved.",

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AU - Kim, Jang Kyoung

AU - Kim, Yong Hee

N1 - Funding Information: This work was partially supported by grants from the National Research Foundation of Korea (2013030789), the Brain Korea 21 plus program (22A20130011095), and the Korean Health Technology R&D project through the Ministry of Health & Welfare (HI13C-1938-010013). All the confocal microscopy and Cellvizio imaging experiments were carried out at Korea Basic Science Institute, Chuncheon Center, Chuncheon-city, Korea. We are sincerely grateful for their assistance in performing experiments and data analysis. Publisher Copyright: © 2014 Macmillan Publishers Limited. All rights reserved.

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N2 - Commercial anti-obesity drugs acting in the gastrointestinal tract or the central nervous system have been shown to have limited efficacy and severe side effects. Anti-obesity drug development is thus focusing on targeting adipocytes that store excess fat. Here, we show that an adipocyte-targeting fusion-oligopeptide gene carrier consisting of an adipocyte-targeting sequence and 9-arginine (ATS-9R) selectively transfects mature adipocytes by binding to prohibitin. Injection of ATS-9R into obese mice confirmed specific binding of ATS-9R to fat vasculature, internalization and gene expression in adipocytes. We also constructed a short-hairpin RNA (shRNA) for silencing fatty-acid-binding protein 4 (shFABP4), a key lipid chaperone in fatty-acid uptake and lipid storage in adipocytes. Treatment of obese mice with ATS-9R/shFABP4 led to metabolic recovery and body-weight reduction (>20%). The ATS-9R/shFABP4 oligopeptide complex could prove to be a safe therapeutic approach to regress and treat obesity as well as obesity-induced metabolic syndromes.

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Oligopeptide complex for targeted non-viral gene delivery to adipocytes

Abstract

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