Research press release


Nature Materials

Gene delivery to fat cells



今回、Yong-Hee Kimたちは、脂肪細胞を標的化するための配列を持つ短いペプチドと天然アミノ酸アルギニンからなる遺伝子キャリアを開発した。そして、成熟脂肪細胞の表面に見られるタンパク質と遺伝子キャリアが結合することによって、選択的に遺伝物質を成熟脂肪細胞に送達できることを示した。Kimたちは、この遺伝子キャリアを肥満マウスに適用することによって、遺伝子キャリアと脂肪血管系が特異的に結合し、脂肪細胞において細胞内移行と遺伝子発現が起こることを見いだした。さらに、治療遺伝子(脂肪酸結合タンパク質4の発現を抑制する短いヘアピンRNAからなる)が遺伝子キャリアと結び付いたオリゴペプチド複合体を肥満マウスに注射することによって、代謝回復と20%以上の体重減少が起こることを明らかにした。

A peptide-based gene carrier that specifically targets fat cells in a mouse model of obesity can deliver a therapeutic gene, which helps reduce body weight, reports a paper published online this week in Nature Materials. Although future studies are needed to test its feasibility and safety in humans, the molecular complex could be used to treat obesity and obesity-induced metabolic syndromes.

Obesity is often a result of over-eating, which results in the storage of energy in fat tissue. Therefore, fat tissue is a target for anti-obesity therapies, but in the case of gene delivery systems, it has not been possible to apply gene therapy to fat cells because the cells are difficult to transfect.

Yong-Hee Kim and colleagues created a gene carrier that comprises a short peptide with a gene sequence for targeting fat cells and the natural amino acid, arginine. They show that this gene carrier can selectively deliver genetic material to mature fat cells by binding to a protein found on the surface of the cells. The authors find that injecting these gene carriers into obese mice results in specific binding of the gene carrier to fat vasculature, followed by internalization and gene expression in the fat cells. The incorporation of a therapeutic gene (composed of a short hairpin RNA for silencing fatty-acid-binding protein-4) results in the formation of an oligopeptide complex. Kim and colleagues found that when they injected this oligopeptide complex into obese mice, it led to metabolic recovery and body-weight reduction greater than 20%.

doi: 10.1038/nmat4092


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