Protein Delivery Using Cys2鈥揌is2 Zinc-Finger Domains

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• 作者：Thomas Gaj ; Jia Liu ; Kimberly E. Anderson ; Shannon J. Sirk ; Carlos F. Barbas ; III
• 刊名：ACS Chemical Biology
• 出版年：2014
• 出版时间：August 15, 2014
• 年：2014
• 卷：9
• 期：8
• 页码：1662-1667
• 全文大小：411K
• ISSN：1554-8937

文摘

The development of new methods for delivering proteins into cells is a central challenge for advancing both basic research and therapeutic applications. We previously reported that zinc-finger nuclease proteins are intrinsically cell-permeable due to the cell-penetrating activity of the Cys₂鈥揌is₂ zinc-finger domain. Here, we demonstrate that genetically fused zinc-finger motifs can transport proteins and enzymes into a wide range of primary and transformed mammalian cell types. We show that zinc-finger domains mediate protein uptake at efficiencies that exceed conventional protein transduction systems and do so without compromising enzyme activity. In addition, we demonstrate that zinc-finger proteins enter cells primarily through macropinocytosis and facilitate high levels of cytosolic delivery. These findings establish zinc-finger proteins as not only useful tools for targeted genome engineering but also effective reagents for protein delivery.