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.
authors.affiliation: 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.
authors.forename: Young-Wook
authors.initials: YW
authors.lastname: Won
authors.affiliation: Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Partho Protim
authors.initials: PP
authors.lastname: Adhikary
authors.affiliation: Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Kwang Suk
authors.initials: KS
authors.lastname: Lim
authors.affiliation: Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Hyung Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Jang Kyoung
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Yong-Hee
authors.initials: YH
authors.lastname: Kim
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D050556:Fatty Acid-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005227:Fatty Acids / Q000493:pharmacokinetics; D015870:Gene Expression; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000091402:Prohibitins; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D014162:Transfection / Q000379:methods
chemical_list: C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D009842:Oligopeptides; D000091402:Prohibitins; D034741:RNA, Small Interfering; D012097:Repressor Proteins