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–His2 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.

Thomas Gaj

Jia Liu

Kimberly E. Anderson

Shannon J. Sirk

Carlos F. Barbas

ACS Chemical Biology

ACS 化学生物学为广泛涵盖化学和生物学之间接口的研究提供了一个快速交流的国际论坛。该期刊还作为一个论坛，促进生物学家和化学家之间的交流，从而转化为新的研究机会和发现。将发表结果，其中分子推理已被用于通过体外研究、细胞生物学方法或有机体研究来探索问题。我们欢迎对蛋白质、核酸、糖、脂质和非生物聚合物的机械研究。该杂志服务于一个大型科学界，从化学和生物学角度探索细胞功能。据了解，提交的作品是基于原始结果，之前没有发表过。

ACS Chemical Biology provides an international forum for rapid communication of research that broadly encompasses the interface between chemistry and biology. The journal serves as a platform to facilitate interactions between biologists and chemists, leading to new research opportunities and discoveries. We welcome the publication of results where molecular reasoning has been applied to explore problems through in vitro studies, cell biology methods, or organismal research. We particularly encourage mechanistic studies on proteins, nucleic acids, carbohydrates, lipids, and non-biological polymers. This journal serves a large scientific community that explores cellular functions from both chemical and biological perspectives. Please note that submitted works must be based on original results and have not been previously published.

ACS Chemical Biology 是一个国际论坛，广泛涵盖化学与生物学交叉领域的研究。该期刊旨在促进生物学家与化学家之间的交流，从而催生新的研究机会和发现。我们欢迎发表利用分子推理，通过体外研究、细胞生物学方法或有机体研究探索问题的研究成果。我们特别关注对蛋白质、核酸、糖、脂质及非生物聚合物的机制研究。该期刊服务于一个庞大的科学社区，致力于从化学和生物学的角度探索细胞功能。请注意，提交的作品必须基于原创结果，且未曾发表过。

Protein Delivery Using Cys<sub>2</sub>–His<sub>2</sub> Zinc-Finger Domains

It is demonstrated that genetically fused zinc-finger motifs can transport proteins and enzymes into a wide range of primary and transformed mammalian cell types and mediate protein uptake at efficiencies that exceed conventional protein transduction systems and do so without compromising enzyme activity.

Category	Quartile
生物学	2
生物学, 生化与分子生物学	3

Protein Delivery Using Cys₂–His₂ Zinc-Finger Domains

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Journal Info

Category	Quartile
BIOCHEMISTRY & MOLECULAR BIOLOGY	2

Protein Delivery Using Cys2–His2 Zinc-Finger Domains

ivySCI AI Smartly Parses PDF, Answers Researchers' Questions, and Helps You Understand Papers in Seconds

Journal Info

Protein Delivery Using Cys₂–His₂ Zinc-Finger Domains