Oligopeptide complex for targeted non-viral gene delivery to adipocytes
- Authors
- Won, Young-Wook; Adhikary, Partho Protim; Lim, Kwang Suk; Kim, Hyung Jin; Kim, Jang Kyoung; Kim, Yong-Hee
- Issue Date
- Dec-2014
- Publisher
- NATURE RESEARCH
- Citation
- NATURE MATERIALS, v.13, no.12, pp.1157 - 1164
- Indexed
- SCIE
SCOPUS
- Journal Title
- NATURE MATERIALS
- Volume
- 13
- Number
- 12
- Start Page
- 1157
- End Page
- 1164
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/158463
- DOI
- 10.1038/NMAT4092
- ISSN
- 1476-1122
- Abstract
- Commercial anti-obesity drugs acting in the gastrointestinal tract or the central nervous system have been shown to have limited effcacy 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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