鋅指核酸酶 （英語：Zinc-finger nucleases, ZFNs ），是人工改造的限制酶 ，通過融合鋅指結構 的結合DNA結構域 和分解DNA結構域而成。可通過基因工程改造鋅指結構域使鋅指核酸酶針對複雜基因組裏的特定DNA序列。藉助內源DNA的修復機制，鋅指核酸酶可以精確改變高等動物的基因組。類似的技術還有類轉錄活化因子核酸酶 。
鋅指核酸酶是一種特定於位點的核酸限制內切酶
功能：設計在特定的位置來結合併分解DNA，含有兩個蛋白質結構域 。
第一個結構域是DNA結合結構域，其由真核轉錄因子 並包含鋅指所構成；第二個結構域是核酸酶結構域，它由FokI 限制酶構成，並負責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 核酸內切酶 FokI 的非特異分解域經常被用做 ZFNs 的分解域，[ 2] [ 3] [ 4]
幾個不同的蛋白質工程 技術已經用來提高用於ZFNs核酸酶域的活性和特異性。直接進化 被用來產生FokI的多樣性以增強被作者稱為"Sharkey"的[ 5] [ 6] [ 7] [ 8] [ 9]
^ 引用錯誤：沒有為名為genomeengineering的參考文獻提供內容 Guo, Jing; Gaj, Thomas; Barbas, Carlos F. Directed Evolution of an Enhanced and Highly Efficient FokI Cleavage Domain for Zinc Finger Nucleases. Journal of Molecular Biology (Elsevier BV). 2010, 400 (1): 96–107. ISSN 0022-2836 doi:10.1016/j.jmb.2010.04.060 Miller, Jeffrey C; Holmes, Michael C; Wang, Jianbin; Guschin, Dmitry Y; Lee, Ya-Li; Rupniewski, Igor; Beausejour, Christian M; Waite, Adam J; Wang, Nathaniel S; Kim, Kenneth A; Gregory, Philip D; Pabo, Carl O; Rebar, Edward J. An improved zinc-finger nuclease architecture for highly specific genome editing . Nature Biotechnology (Springer Nature). 2007, 25 (7): 778–785. ISSN 1087-0156 doi:10.1038/nbt1319 Doyon, Yannick; Vo, Thuy D; Mendel, Matthew C; Greenberg, Shon G; Wang, Jianbin; Xia, Danny F; Miller, Jeffrey C; Urnov, Fyodor D; Gregory, Philip D; Holmes, Michael C. Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures. Nature Methods (Springer Nature). 2010-12-05, 8 (1): 74–79. ISSN 1548-7091 doi:10.1038/nmeth.1539 Ramalingam, Sivaprakash; Kandavelou, Karthikeyan; Rajenderan, Raja; Chandrasegaran, Srinivasan. Creating Designed Zinc-Finger Nucleases with Minimal Cytotoxicity. Journal of Molecular Biology (Elsevier BV). 2011, 405 (3): 630–641. ISSN 0022-2836 doi:10.1016/j.jmb.2010.10.043
Mandell JG, Barbas CF. Zinc Finger Tools: custom DNA-binding domains for transcription factors and nucleases . Nucleic Acids Res. July 2006, 34 (Web Server issue): W516–23 [2009-09-25 ] . PMC 1538883 PMID 16845061 doi:10.1093/nar/gkl209 存檔 於2019-07-10）. Porteus MH, Carroll D. Gene targeting using zinc finger nucleases . Nat. Biotechnol. August 2005, 23 (8): 967–73. PMID 16082368 doi:10.1038/nbt1125 Doyon Y, McCammon JM, Miller JC; et al. Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases . Nat. Biotechnol. June 2008, 26 (6): 702–8. PMC 2674762 PMID 18500334 doi:10.1038/nbt1409 Meng X, Noyes MB, Zhu LJ, Lawson ND, Wolfe SA. Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases . Nat. Biotechnol. June 2008, 26 (6): 695–701. PMC 2502069 PMID 18500337 doi:10.1038/nbt1398 
