Oligopeptide complex for targeted non-viral gene delivery to adipocytes

  • Nat Mater. 2014 Dec;13(12):1157-64. doi: 10.1038/nmat4092.
Young-Wook Won  1 ,  Partho Protim Adhikary  2 ,  Kwang Suk Lim  2 ,  Hyung Jin Kim  2 ,  Jang Kyoung Kim  2 ,  Yong-Hee Kim  2
Affiliations
  • 1. 1] Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul 133-791, Republic of Korea [2] Division of Cardiothoracic Surgery, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.
  • 2. Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul 133-791, Republic of Korea.
PMID: 25282508 DOI: 10.1038/nmat4092
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.

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