Oligopeptide complex for targeted non-viral gene delivery to adipocytes

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

Research output: Contribution to journalArticle

63 Citations (Scopus)

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 languageEnglish
Pages (from-to)1157-1164
Number of pages8
JournalNature Materials
Volume13
DOIs
Publication statusPublished - Dec 2014

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    Won, Y-W., Adhikary, P., Lim, K. S., Kim, H. J., Kim, J. K., & Kim, Y-H. (2014). Oligopeptide complex for targeted non-viral gene delivery to adipocytes. Nature Materials, 13, 1157-1164. https://doi.org/10.1038/nmat4092