Protein delivery using Cys2-His2 zinc-finger domains

Thomas Gaj, Jia Liu, Kimberly E. Anderson, Shannon J. Sirk, Carlos F. Barbas

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1662-1667
Number of pages6
JournalACS chemical biology
Issue number8
StatePublished - Aug 15 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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