Nat Commun: Dual Receptor Mediated Accurate Gene Interference Technology
November 29, 2016 Source: Bio Valley
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];On November 24th, 2016, Nature Communications published a research paper by Prof. Qi Xianxian from the School of Chemistry and Chemical Engineering of Nanjing University. This paper proposes a dual receptor-mediated precision gene interference technology and a new treatment for cancer.
Gene interference technology has important medical value in the treatment of human diseases. The technology utilizes a specific vector to carry siRNA into target cells, selectively silencing the target gene, thereby inhibiting protein synthesis, inducing apoptosis, and achieving disease treatment. Efficient and highly specific delivery of siRNA to target cells is the key to achieving gene interference therapy.
Conventional siRNA delivery systems commonly use antibodies or nucleic acid aptamers as recognition molecules to bind to a single receptor on the cell surface to achieve a targeted function. Since receptors with high expression on the surface of tumor cells may also be expressed on the surface of normal cells, it is difficult to ensure precise targeting of transport by single receptor recognition. In response to this critical issue, Professor Qi Xianxian's research team used the aptamer sgc8c and sgc4f to bind to two specific receptors on the cell surface to form a double-locked structure, and developed a dual receptor-mediated siRNA delivery system. Differentiation of cell subtypes, as well as low toxicity and efficient siRNA delivery.
The method firstly designed and synthesized a nucleic acid nanocarrier containing siRNA by DNA self-assembly, and one end of the hairpin structure. The loop of the hairpin is a substrate for zinc ion-dependent DNase. The carrier has the advantages of good serum stability, small cytotoxicity, carrying ability and high escape ability of endosomes. When the carrier and the cell surface-bound sgc8c and sgc4f meet, the zinc ion-dependent DNase at one end of the aptamer sgc4f catalyzes the cleavage of the hairpin structure on the carrier to form a single DNA strand. This single strand further opens the hairpin on the aptamer sgc8c, and siRNA is carried into the target cell by sgc8c (Fig. 1). For cells that bind only to a nucleic acid aptamer of sgc8c or sgc4f, the delivery system is inactive, thereby reducing off-targeting.
This study provides new ideas for efficient, highly specific siRNA delivery and precise treatment of cancer.
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