锌指核酸酶 （英語：Zinc-finger nucleases, ZFNs ），是人工改造的限制酶 ，通过融合锌指结构 的结合DNA结构域 和分解DNA结构域而成。可通过基因工程改造锌指结构域使锌指核酸酶针对复杂基因组里的特定DNA序列。借助内源DNA的修复机制，锌指核酸酶可以精确改变高等动物的基因组。類似的技術還有類轉錄活化因子核酸酶 。
锌指核酸酶是一种特定于位点的核酸限制内切酶
功能：设计在特定的位置来结合并分解DNA，含有两个蛋白质结构域 。
第一个结构域是DNA结合结构域，其由真核转录因子 并包含锌指所构成；第二个结构域是核酸酶结构域，它由FokI 限制酶构成，并负责DNA的催化分解。
A pair of two ZFNs with three zinc fingers each are shown introducing a double-strand break. Subsequent to this, the double strand break is being repaired through either homologous recombination or non-homologous end joining.[ 1] type IIs 核酸内切酶 FokI 的非特异分解域经常被用做 ZFNs 的分解域，[ 2] [ 3] [ 4]
几个不同的蛋白质工程 技术已经用来提高用于ZFNs核酸酶域的活性和特异性。直接进化 被用来产生FokI的多样性以增强被作者称为"Sharkey"的[ 5] [ 6] [ 7] [ 8] [ 9]
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