Zinc-finger nucleases (ZFNs) are versatile reagents that have redefined genome
engineering. Realizing the full potential of this technology requires the development of safe
and effective methods for delivering ZFNs into cells. We demonstrate the intrinsic cell-
penetrating capabilities of the standard ZFN architecture and show that direct delivery of
ZFNs as proteins leads to efficient endogenous gene disruption in various mammalian cell
types with minimal off-target effects.