锌指核酸酶的构建及其在动物基因组编辑中的应用
|
摘要
精确高效的实现内源基因靶向编辑是转基因技术的难点和重点。传统的自发同源重组方法的效率低下和逆病毒载体法的安全性差等问题，限制其广泛应用和转基因新品种的培育。锌指核酸酶作为一种人工核酸酶，含有特异DNA识别结构域锌指蛋白和非特异性DNA切割活性域FokⅠ，赋予了其靶向切割特定DNA双链的能力。当锌指核酸酶识别并结合至靶序列，以二聚体形式切割DNA产生双链切口（Double strand breaks,DSBs）。细胞在修复DSBs过程中功能实现基因组的靶向编辑，如基因敲入（Geneknock-in），基因敲除（Gene knock-out）,基因修复（Gene correction），基因破坏（Genedisruption）等。
锌指蛋白是决定锌指核酸酶结合靶基因特异性和基因修饰高效性的关键因素。现阶段，主要是组装、筛选获得特异锌指蛋白，然后与FokⅠ连接获得活性锌指核酸酶。有研究表明，即使获得的锌指蛋白有DNA识别和结合活性，组装成锌指核酸酶仍然不能切割靶序列。所以，获得活性锌指核酸酶是此技术的难点。此外，锌指核酸酶实现基因组编辑后，如何筛选和富集阳性克隆，获得转基因细胞系也是锌指核酸酶技术应用的关键之一。本论文以奶山羊编码酪蛋白的alpha S1-casein（α S1-casein）为靶基因，利用酵母筛选系统，从锌指核酸酶文库中直接筛选获得活性锌指核酸酶，然后在哺乳动物细胞水平检测锌指核酸酶切割靶序列的活性。最后将锌指核酸酶作用于靶细胞，通过嘌呤霉素药物筛选富集作用，获得基因敲除细胞系，为后续获得转基因奶山羊新品种提供技术支持。同时，基于锌指蛋白和FokⅠ相互作用的独立性，构建了锌指核酸酶介导的酵母杂交系统，为鉴定蛋白与蛋白相互作用提供一种新方法。
1．基于开源式（OPEN）筛选方法，构建3个锌指核酸酶随机突变文库。每个文库的三个锌指模块中，一个单锌指模块中识别DNA的关键氨基酸的编码序列以PCR方式实现随机突变，并保持其他两个模块不变，以质粒形式的锌指核酸酶文库库容量达到106~107。根据靶基因α S1-casein的潜在靶序列和OPEN筛选方法，构建9个报告载体。
2.基于Gal4蛋白介导的酵母双杂交筛选系统，第一轮筛选富集识别6个三联碱基的单个锌指，将富集的单锌指组装成2个锌指核酸酶重组文库；然后通过第二轮的筛选，获得识别左右单侧9-bp的活性锌指核酸酶；最后通过第三轮针对全长靶序列的筛选，获得3对活性锌指核酸酶。
3.构建锌指核酸酶真核表达载体对pST-ZFNL、pST-ZFNR和含靶序列的双荧光报告载体pRFP-EGFP-BS，检测锌指核酸酶在哺乳动物细胞内的切割活性。将锌指核酸酶表达载体和双荧光报告载体共转染至HEK293T细胞。当锌指核酸酶作用于EGFP基因中的靶序列，修复突变的EGFP基因，细胞表现出绿色荧光阳性。利用流式细胞仪检测锌指核酸酶作用后的绿色荧光阳性细胞率，间接反应筛选获得的3对锌指核酸酶切割靶序列活性分别为8.9%，9.3%，5.0%。
4.活性锌指核酸酶作用于靶细胞——奶山羊乳腺上皮细胞。将锌指核酸酶载体和报告载体pB-CBA-Puro-BS共同电转染至奶山羊乳腺上皮细胞。基于嘌呤霉素抗性基因的报告载体含有靶序列，当锌指核酸酶切割靶序列，修复报告基因后，细胞在含嘌呤霉素药物的培养基中存活，实现阳性细胞的筛选和富集。然后收集阳性克隆，利用T7核酸内切酶分析基因组中靶序列突变频率。当无报告载体pB-CBA-Puro-BS的富集作用时，我们未检测到基因组靶序列的突变；有报告载体时，利用嘌呤霉素药物筛选富集获得细胞克隆，3对锌指核酸酶实现靶基因突变率分别为9.4%，15.9%和4.1%。
5.锌指核酸酶的锌指蛋白ZFP和FokⅠ切割域各司其职，具有相互独立性。将ZFP和X蛋白融合表达，FokⅠ和Y蛋白融合表达，利用X和Y蛋白的相互作用募集ZFP和FokⅠ，形成有活性的重组ZFN，切割靶序列，实现下游报告基因的表达。基于Gal4基因的报告载体，我们验证了蛋白对P53/SV40LT募集活性ZFN，随后利用此系统在cDNA文库中筛选和WDSV的orfA相互作用的蛋白。ZFN介导的此酵母双杂交系统为蛋白与蛋白相互作用鉴定提供一种新方法。
Precisely and highly efficient modification of endogenous genes is one of the mostimportant issues in the development of transgenic technology. Two major traditional methods,spontaneous recombination with extremely low efficiency (1×106) and retrovirus mediatedgene target with concern of safety are limited in wide application and development oftransgenic breeding technology. As an artificial nuclease, zinc finger nuclease (ZFN) iscomposed of a DNA binding domain of zinc finger protein (ZFP) and non-specific DNAcleavage domain of FokⅠ. A pair of ZFN as a dimer cut target locus in genome, resulting inDSBs. In the process of DSBs repair, genomic editing is accomplished, for instance, targetedgene knock-in, gene knock-out, gene correction, gene disruption.
The cleavage specificity efficiency of ZFN is largely determined by zinc finger proteins.Currently, zinc finger proteins were obtained via modular assembly or library screeningsystem, then fused to FokⅠ to generate active ZFNs target sites of interest. Whereas, ZFNsalways failed to cut target site, even the ZFPs had ability to recognize and bind DNA targetsites. Thus, obtaining active ZFNs is an urgent issue about this technology. In addition, how toenrich positive cells with gene-modification and obtain transgenic cell lines are crucial to theapplication of ZFNs.
Previous studies all focused on achievement of specific ZFPs. In this study, we created ayeast-based screening system to obtain ZFNs directly. Goat alpha S1-casein gene as a safeharbor and target gene for generation of transgenic cell lines. According to the target sequence,active ZFNs were screened from randomized ZFNs libraries via yeast-based screening system.Then, activities of screened ZFNs were validated in human HEK293T cells. Finally, ZFNs cutalpha S1-casein gene in target cells. Under the pressure of puromycin, positive cells wereenriched after ZFN treatment and cells with target gene modified were achieved.
1. According to the OPEN method, three randomized ZFN libraries were constructedusing PCR with randomized primers. In each library, sequences encoding the key amino acidsin one motif were randomized; the other two zinc finger motifs were maintained with thestandard frame. On the level of plasmid, the complexity of each library was about106~107independent colonies. Meanwhile, nine reporter vectors were constructed harboring potential target sequence of goat α S1-casein gene.
2. The yeast screening system was based on Gal4protein, in which three-step screeninginvolved. The first step screening aimed to enrich six single finger motif bind to each triplet(3-bp). Enriched single motifs were assembled together to generate two reconstructed ZFNlibraries. ZFNs target9-bp left or right half sites were obtained through the second stepscreening. Finally, three pairs of active ZFNs target full site were achieved via the third stepscreening.
3. To detect activities of screened ZFN pairs, ZFN mammalian expression vectorspST-ZFNL, pST-ZFNR and reporter plasmid containing pRFP-EGFP-BS two fluorescentgenes were constructed. ZFNs expression vectors and reporter plasmids were co-transfectedinto HEK293T cells. Upon ZFNs cut target site in EGFP gene, which was restored duringDSBs repair and green fluorescence cells were observed. The rate of EGFP-positive cellsindicated cleavage activity of ZFNs. Then, the three pairs of ZFNs activities were8.9%,9.3%,5.0%, respectively.
4. Active ZFNs worked in target cells—goat mammalian epithelial cells. ZFNsexpression vectors and another reporter vector pB-CBA-Puro-BS were co-electroporated intotarget cells. Upon ZFN-mediated cleavage at target site on reporter, puromycin resistant genewas restored to enrich positive cells. Thus, clones survived in the medium with highconcentration of puromycin. Genomes of treated cell were isolated, and target sequences wereamplified using PCR. T7endonuclease I assay was performed to analyze mutation rate oftarget gene. No insertions or deletions were detected without puromycin enrichment system.Nevertheless, mutations were observed under puromycin selection pressure in the enrichmenteffect of reporter system. Finally, gene mutation rates of three pairs ZFNs generated in targetcells were9.4%,15.9%,4.1%, respectively.
5. ZFN consists of two separably functional domains, DNA banding domain (zinc fingerprotein) and nuclease domain (FokⅠ). The bait protein is fused with a zinc finger protein anda prey is expressed as fusion protein with FokⅠ. A unique intermediate reporter vector isdesigned such that Gal4transcription factor gene is disrupted by the ZFN target sequenceflanked by two short repeats. The interaction of bait and prey proteins reconstitutes the ZFNfunction, resulting in double strand break (DSB) on its target sequence. The DSB activatescellular DNA repair system, leading to restoring a functional Gal4transcriptional factor whichcan activate reporter genes, His3, Ade2, LacZ in AH109yeast strain. This system can betheoretically used to any type of cellular proteins. Additionally, by using intermediate reportergene Gal4, the interaction signal is amplified. This novel system will provide an additionaltool for the technologies of protein interactomics.
锌指蛋白是决定锌指核酸酶结合靶基因特异性和基因修饰高效性的关键因素。现阶段，主要是组装、筛选获得特异锌指蛋白，然后与FokⅠ连接获得活性锌指核酸酶。有研究表明，即使获得的锌指蛋白有DNA识别和结合活性，组装成锌指核酸酶仍然不能切割靶序列。所以，获得活性锌指核酸酶是此技术的难点。此外，锌指核酸酶实现基因组编辑后，如何筛选和富集阳性克隆，获得转基因细胞系也是锌指核酸酶技术应用的关键之一。本论文以奶山羊编码酪蛋白的alpha S1-casein（α S1-casein）为靶基因，利用酵母筛选系统，从锌指核酸酶文库中直接筛选获得活性锌指核酸酶，然后在哺乳动物细胞水平检测锌指核酸酶切割靶序列的活性。最后将锌指核酸酶作用于靶细胞，通过嘌呤霉素药物筛选富集作用，获得基因敲除细胞系，为后续获得转基因奶山羊新品种提供技术支持。同时，基于锌指蛋白和FokⅠ相互作用的独立性，构建了锌指核酸酶介导的酵母杂交系统，为鉴定蛋白与蛋白相互作用提供一种新方法。
1．基于开源式（OPEN）筛选方法，构建3个锌指核酸酶随机突变文库。每个文库的三个锌指模块中，一个单锌指模块中识别DNA的关键氨基酸的编码序列以PCR方式实现随机突变，并保持其他两个模块不变，以质粒形式的锌指核酸酶文库库容量达到106~107。根据靶基因α S1-casein的潜在靶序列和OPEN筛选方法，构建9个报告载体。
2.基于Gal4蛋白介导的酵母双杂交筛选系统，第一轮筛选富集识别6个三联碱基的单个锌指，将富集的单锌指组装成2个锌指核酸酶重组文库；然后通过第二轮的筛选，获得识别左右单侧9-bp的活性锌指核酸酶；最后通过第三轮针对全长靶序列的筛选，获得3对活性锌指核酸酶。
3.构建锌指核酸酶真核表达载体对pST-ZFNL、pST-ZFNR和含靶序列的双荧光报告载体pRFP-EGFP-BS，检测锌指核酸酶在哺乳动物细胞内的切割活性。将锌指核酸酶表达载体和双荧光报告载体共转染至HEK293T细胞。当锌指核酸酶作用于EGFP基因中的靶序列，修复突变的EGFP基因，细胞表现出绿色荧光阳性。利用流式细胞仪检测锌指核酸酶作用后的绿色荧光阳性细胞率，间接反应筛选获得的3对锌指核酸酶切割靶序列活性分别为8.9%，9.3%，5.0%。
4.活性锌指核酸酶作用于靶细胞——奶山羊乳腺上皮细胞。将锌指核酸酶载体和报告载体pB-CBA-Puro-BS共同电转染至奶山羊乳腺上皮细胞。基于嘌呤霉素抗性基因的报告载体含有靶序列，当锌指核酸酶切割靶序列，修复报告基因后，细胞在含嘌呤霉素药物的培养基中存活，实现阳性细胞的筛选和富集。然后收集阳性克隆，利用T7核酸内切酶分析基因组中靶序列突变频率。当无报告载体pB-CBA-Puro-BS的富集作用时，我们未检测到基因组靶序列的突变；有报告载体时，利用嘌呤霉素药物筛选富集获得细胞克隆，3对锌指核酸酶实现靶基因突变率分别为9.4%，15.9%和4.1%。
5.锌指核酸酶的锌指蛋白ZFP和FokⅠ切割域各司其职，具有相互独立性。将ZFP和X蛋白融合表达，FokⅠ和Y蛋白融合表达，利用X和Y蛋白的相互作用募集ZFP和FokⅠ，形成有活性的重组ZFN，切割靶序列，实现下游报告基因的表达。基于Gal4基因的报告载体，我们验证了蛋白对P53/SV40LT募集活性ZFN，随后利用此系统在cDNA文库中筛选和WDSV的orfA相互作用的蛋白。ZFN介导的此酵母双杂交系统为蛋白与蛋白相互作用鉴定提供一种新方法。
Precisely and highly efficient modification of endogenous genes is one of the mostimportant issues in the development of transgenic technology. Two major traditional methods,spontaneous recombination with extremely low efficiency (1×106) and retrovirus mediatedgene target with concern of safety are limited in wide application and development oftransgenic breeding technology. As an artificial nuclease, zinc finger nuclease (ZFN) iscomposed of a DNA binding domain of zinc finger protein (ZFP) and non-specific DNAcleavage domain of FokⅠ. A pair of ZFN as a dimer cut target locus in genome, resulting inDSBs. In the process of DSBs repair, genomic editing is accomplished, for instance, targetedgene knock-in, gene knock-out, gene correction, gene disruption.
The cleavage specificity efficiency of ZFN is largely determined by zinc finger proteins.Currently, zinc finger proteins were obtained via modular assembly or library screeningsystem, then fused to FokⅠ to generate active ZFNs target sites of interest. Whereas, ZFNsalways failed to cut target site, even the ZFPs had ability to recognize and bind DNA targetsites. Thus, obtaining active ZFNs is an urgent issue about this technology. In addition, how toenrich positive cells with gene-modification and obtain transgenic cell lines are crucial to theapplication of ZFNs.
Previous studies all focused on achievement of specific ZFPs. In this study, we created ayeast-based screening system to obtain ZFNs directly. Goat alpha S1-casein gene as a safeharbor and target gene for generation of transgenic cell lines. According to the target sequence,active ZFNs were screened from randomized ZFNs libraries via yeast-based screening system.Then, activities of screened ZFNs were validated in human HEK293T cells. Finally, ZFNs cutalpha S1-casein gene in target cells. Under the pressure of puromycin, positive cells wereenriched after ZFN treatment and cells with target gene modified were achieved.
1. According to the OPEN method, three randomized ZFN libraries were constructedusing PCR with randomized primers. In each library, sequences encoding the key amino acidsin one motif were randomized; the other two zinc finger motifs were maintained with thestandard frame. On the level of plasmid, the complexity of each library was about106~107independent colonies. Meanwhile, nine reporter vectors were constructed harboring potential target sequence of goat α S1-casein gene.
2. The yeast screening system was based on Gal4protein, in which three-step screeninginvolved. The first step screening aimed to enrich six single finger motif bind to each triplet(3-bp). Enriched single motifs were assembled together to generate two reconstructed ZFNlibraries. ZFNs target9-bp left or right half sites were obtained through the second stepscreening. Finally, three pairs of active ZFNs target full site were achieved via the third stepscreening.
3. To detect activities of screened ZFN pairs, ZFN mammalian expression vectorspST-ZFNL, pST-ZFNR and reporter plasmid containing pRFP-EGFP-BS two fluorescentgenes were constructed. ZFNs expression vectors and reporter plasmids were co-transfectedinto HEK293T cells. Upon ZFNs cut target site in EGFP gene, which was restored duringDSBs repair and green fluorescence cells were observed. The rate of EGFP-positive cellsindicated cleavage activity of ZFNs. Then, the three pairs of ZFNs activities were8.9%,9.3%,5.0%, respectively.
4. Active ZFNs worked in target cells—goat mammalian epithelial cells. ZFNsexpression vectors and another reporter vector pB-CBA-Puro-BS were co-electroporated intotarget cells. Upon ZFN-mediated cleavage at target site on reporter, puromycin resistant genewas restored to enrich positive cells. Thus, clones survived in the medium with highconcentration of puromycin. Genomes of treated cell were isolated, and target sequences wereamplified using PCR. T7endonuclease I assay was performed to analyze mutation rate oftarget gene. No insertions or deletions were detected without puromycin enrichment system.Nevertheless, mutations were observed under puromycin selection pressure in the enrichmenteffect of reporter system. Finally, gene mutation rates of three pairs ZFNs generated in targetcells were9.4%,15.9%,4.1%, respectively.
5. ZFN consists of two separably functional domains, DNA banding domain (zinc fingerprotein) and nuclease domain (FokⅠ). The bait protein is fused with a zinc finger protein anda prey is expressed as fusion protein with FokⅠ. A unique intermediate reporter vector isdesigned such that Gal4transcription factor gene is disrupted by the ZFN target sequenceflanked by two short repeats. The interaction of bait and prey proteins reconstitutes the ZFNfunction, resulting in double strand break (DSB) on its target sequence. The DSB activatescellular DNA repair system, leading to restoring a functional Gal4transcriptional factor whichcan activate reporter genes, His3, Ade2, LacZ in AH109yeast strain. This system can betheoretically used to any type of cellular proteins. Additionally, by using intermediate reportergene Gal4, the interaction signal is amplified. This novel system will provide an additionaltool for the technologies of protein interactomics.
引文
Ambrosoli R, di Stasio L, Mazzocco P.1988. Content of αs1-Casein and Coagulation Properties in Goat Milk.Journal of Dairy Science,71(1):24-28.
Aronheim A, Zandi E, Hennemann H, Elledge S J, Karin M.1997. Isolation of an AP-1repressor by a novelmethod for detecting protein-protein interactions. Molecular and cellular biology,17(6):3094-3102.
Bae K-H, Do Kwon Y, Shin H-C, Hwang M-S, Ryu E-H, Park K-S, Yang H-Y, Lee D-k, Lee Y, Park J, SunKwon H, Kim H-W, Yeh B-I, Lee H-W, Hyung Sohn S, Yoon J, Seol W, Kim J-S.2003. Human zincfingers as building blocks in the construction of artificial transcription factors. Nat Biotech,21(3):275-280.
Bedell V M, Wang Y, Campbell J M, Poshusta T L, Starker C G, Krug Ii R G, Tan W, Penheiter S G, Ma A C,Leung A Y H, Fahrenkrug S C, Carlson D F, Voytas D F, Clark K J, Essner J J, Ekker S C.2012. In vivogenome editing using a high-efficiency TALEN system. Nature,491(7422):114-118.
Bellaiche Y, Mogila V, Perrimon N.1999. I-SceI Endonuclease, a New Tool for Studying DNA Double-StrandBreak Repair Mechanisms in Drosophila. Genetics,152(3):1037-1044.
Benabdallah B F, Allard E, Yao S, Friedman G, Gregory P D, Eliopoulos N, Fradette J, Spees J L, Haddad E,Holmes M C, Beausejour C M.2010. Targeted gene addition to human mesenchymal stromal cells as acell-based plasma-soluble protein delivery platform. Cytotherapy,12(3):394-399.
Beumer K, Bhattacharyya G, Bibikova M, Trautman J K, Carroll D.2006. Efficient Gene Targeting inDrosophila With Zinc-Finger Nucleases. Genetics,172(4):2391-2403.
Beumer K J, Trautman J K, Bozas A, Liu J-L, Rutter J, Gall J G, Carroll D.2008. Efficient gene targeting inDrosophila by direct embryo injection with zinc-finger nucleases. Proceedings of the National Academyof Sciences,105(50):19821-19826.
Bibikova M, Beumer K, Trautman J K, Carroll D.2003. Enhancing Gene Targeting with Designed Zinc FingerNucleases. Science,300(5620):764.
Bibikova M, Carroll D, Segal D J, Trautman J K, Smith J, Kim Y-G, Chandrasegaran S.2001. Stimulation ofHomologous Recombination through Targeted Cleavage by Chimeric Nucleases. Molecular and CellularBiology,21(1):289-297.
Bibikova M, Golic M, Golic K G, Carroll D.2002. Targeted Chromosomal Cleavage and Mutagenesis inDrosophila Using Zinc-Finger Nucleases. Genetics,161(3):1169-1175.
Bitinaite J, Wah D A, Aggarwal A K, Schildkraut I.1998. FokⅠ dimerization is required for DNA cleavage.Proceedings of the National Academy of Sciences,95(18):10570-10575.
Bot A.2010. The Landmark Approval of Provenge (R), What It Means to Immunology and "In This Issue": TheComplex Relation Between Vaccines and Autoimmunity. International Reviews of Immunology,29(3):235-238.
Bozas A, Beumer K J, Trautman J K, Carroll D.2009. Genetic Analysis of Zinc-Finger Nuclease-Induced GeneTargeting in Drosophila. Genetics,182(3):641-651.
Brown R S.2005. Zinc finger proteins: getting a grip on RNA. Current Opinion in Structural Biology,15(1):94-98.
Brunet E, Simsek D, Tomishima M, DeKelver R, Choi V M, Gregory P, Urnov F, Weinstock D M, Jasin M.2009.Chromosomal translocations induced at specified loci in human stem cells. Proceedings of the NationalAcademy of Sciences,106(26):10620-10625.
Cai C, Doyon Y, Ainley W M, Miller J, DeKelver R, Moehle E, Rock J, Lee Y-L, Garrison R, Schulenberg L,Blue R, Worden A, Baker L, Faraji F, Zhang L, Holmes M, Rebar E, Collingwood T, Rubin-Wilson B,Gregory P, Urnov F, Petolino J.2009. Targeted transgene integration in plant cells using designed zincfinger nucleases. Plant Molecular Biology,69(6):699-709.
Cannon P, June C.2011. Chemokine receptor5knockout strategies. Current Opinion in HIV and AIDS,6(1):74-7910.1097/COH.1090b1013e32834122d32834127.
Carroll D.2011. Genome Engineering With Zinc-Finger Nucleases. Genetics,188(4):773-782.
Cebo C, Lopez C, Henry C, Beauvallet C, Ménard O, Bevilacqua C, Bouvier F, Caillat H, Martin P.2012. Goatαs1-casein genotype affects milk fat globule physicochemical properties and the composition of the milkfat globule membrane. Journal of Dairy Science,95(11):6215-6229.
Cermak T, Doyle E L, Christian M, Wang L, Zhang Y, Schmidt C, Baller J A, Somia N V, Bogdanove A J, VoytasD F.2011. Efficient design and assembly of custom TALEN and other TAL effector-based constructs forDNA targeting. Nucleic Acids Research,39(12): e82.
Choo Y, Isalan M.2000. Advances in zinc finger engineering. Current Opinion in Structural Biology,10(4):411-416.
Choo Y, Sanchez-Garcia I, Klug A.1994. In vivo repression by a site-specific DNA-binding protein designedagainst an oncogenic sequence. Nature,372(6507):642-645.
Choulika A, Perrin A, Dujon B, Nicolas J F.1995. Induction of homologous recombination in mammalianchromosomes by using the I-SceI system of Saccharomyces cerevisiae. Molecular and Cellular Biology,15(4):1968-1973.
Christy B, Nathans D.1989. DNA binding site of the growth factor-inducible protein Zif268. Proceedings of theNational Academy of Sciences,86(22):8737-8741.
Clark S, Sherbon J W.2000. Alphas1-casein, milk composition and coagulation properties of goat milk. SmallRuminant Research,38(2):123-134.
Cost G J, Freyvert Y, Vafiadis A, Santiago Y, Miller J C, Rebar E, Collingwood T N, Snowden A, Gregory P D.2010. BAK and BAX deletion using zinc-finger nucleases yields apoptosis-resistant CHO cells.Biotechnology and Bioengineering,105(2):330-340.
Curtin S J, Zhang F, Sander J D, Haun W J, Starker C, Baltes N J, Reyon D, Dahlborg E J, Goodwin M J,Coffman A P, Dobbs D, Joung J K, Voytas D F, Stupar R M.2011. Targeted Mutagenesis of DuplicatedGenes in Soybean with Zinc-Finger Nucleases. Plant Physiology,156(2):466-473.
DeKelver R C, Choi V M, Moehle E A, Paschon D E, Hockemeyer D, Meijsing S H, Sancak Y, Cui X X, SteineE L J, Miller J C, Tam P, Bartsevich V V, Meng X D, Rupniewski I, Gopalan S M, Sun H C, Pitz K J,Rock J M, Zhang L, Davis G D, Rebar E J, Cheeseman I M, Yamamoto K R, Sabatini D M, Jaenisch R,Gregory P D, Urnov F D.2010. Functional genomics, proteomics, and regulatory DNA analysis inisogenic settings using zinc finger nuclease-driven transgenesis into a safe harbor locus in the humangenome. Genome Research,20(8):1133-1142.
Dhanasekaran M, Negi S, Sugiura Y.2005. Designer Zinc Finger Proteins: Tools for Creating ArtificialDNA-Binding Functional Proteins. Accounts of Chemical Research,39(1):45-52.
Dirnberger D, Messerschmid M, Baumeister R.2008. An optimized split-ubiquitin cDNA-library screeningsystem to identify novel interactors of the human Frizzled1receptor. Nucleic Acids Research,36(6): e37.
Doyon Y, McCammon J M, Miller J C, Faraji F, Ngo C, Katibah G E, Amora R, Hocking T D, Zhang L, Rebar EJ, Gregory P D, Urnov F D, Amacher S L.2008. Heritable targeted gene disruption in zebrafish usingdesigned zinc-finger nucleases. Nat Biotech,26(6):702-708.
Doyon Y, Vo T D, Mendel M C, Greenberg S G, Wang J, Xia D F, Miller J C, Urnov F D, Gregory P D, HolmesM C.2011. Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures.Nat Meth,8(1):74-79.
Dreier B, Beerli R R, Segal D J, Flippin J D, Barbas C F.2001. Development of Zinc Finger Domains forRecognition of the5′-ANN-3′Family of DNA Sequences and Their Use in the Construction ofArtificial Transcription Factors. Journal of Biological Chemistry,276(31):29466-29478.
Dreier B, Fuller R P, Segal D J, Lund C V, Blancafort P, Huber A, Koksch B, Barbas C F.2005. Development ofZinc Finger Domains for Recognition of the5′-CNN-3′Family DNA Sequences and Their Use in theConstruction of Artificial Transcription Factors. Journal of Biological Chemistry,280(42):35588-35597.
Drury L1994. Transformation of Bacteria by Electroporation [M]//A. HARWOOD, Protocols for Gene Analysis.Humana Press:1-8.
Durai S, Mani M, Kandavelou K, Wu J, Porteus M H, Chandrasegaran S.2005. Zinc finger nucleases:custom-designed molecular scissors for genome engineering of plant and mammalian cells. Nucleic AcidsResearch,33(18):5978-5990.
Elrod-Erickson M, Rould M A, Nekludova L, Pabo C O.1996. Zif268protein-DNA complex refined at1.6A: amodel system for understanding zinc finger-DNA interactions. Structure (London, England:1993),4(10):1171-1180.
Epinat J C, Arnould S, Chames P, Rochaix P, Desfontaines D, Puzin C, Patin A, Zanghellini A, Paques F, LacroixE.2003. A novel engineered meganuclease induces homologous recombination in yeast and mammaliancells. Nucleic Acids Research,31(11):2952-2962.
Farrell Jr H M, Jimenez-Flores R, Bleck G T, Brown E M, Butler J E, Creamer L K, Hicks C L, Hollar C M,Ng-Kwai-Hang K F, Swaisgood H E.2004. Nomenclature of the Proteins of Cows’ Milk—Sixth Revision.Journal of Dairy Science,87(6):1641-1674.
Feligini M, Frati S, Curik V C, Brambilla A, Parma P, Curik I, Greppi G F, Enne G.2005. Caprine as1-caseinpolymorphism: characterisation of A, B, E and F variants by means of various biochemical and moleculartechniques. Food Technol. Biotechnol,43(123-132.
Fields S, Song O-k.1989. A novel genetic system to detect protein–protein interactions. Nature,340(6230):245-246.
Finn R D, Tate J, Mistry J, Coggill P C, Sammut S J, Hotz H-R, Ceric G, Forslund K, Eddy S R, Sonnhammer EL L, Bateman A.2008. The Pfam protein families database. Nucleic Acids Research,36(suppl1):D281-D288.
Formosa T, Alberts B M.1986. DNA synthesis dependent on genetic recombination: Characterization of areaction catalyzed by purified bacteriophage T4proteins. Cell,47(5):793-806.
Fu F, Sander J D, Maeder M, Thibodeau-Beganny S, Joung J K, Dobbs D, Miller L, Voytas D F.2009. ZincFinger Database (ZiFDB): a repository for information on C2H2zinc fingers and engineered zinc-fingerarrays. Nucleic Acids Research,37(suppl1): D279-D283.
Gaj T, Gersbach C A, Barbas Iii C F.2013. ZFN, TALEN, and CRISPR/Cas-based methods for genomeengineering. Trends in Biotechnology,31(7):397-405.
Galli C, Perota A, Brunetti D, Lagutina I, Lazzari G, Lucchini F.2010. Genetic engineering includingsuperseding microinjection: new ways to make GM pigs. Xenotransplantation,17(6):397-410.
Gamsjaeger R, Liew C K, Loughlin F E, Crossley M, Mackay J P.2007. Sticky fingers: zinc-fingers asprotein-recognition motifs. Trends in biochemical sciences,32(2):63-70.
Geurts A M, Cost G J, Freyvert Y, Zeitler B, Miller J C, Choi V M, Jenkins S S, Wood A, Cui X, Meng X,Vincent A, Lam S, Michalkiewicz M, Schilling R, Foeckler J, Kalloway S, Weiler H, Ménoret S, AnegonI, Davis G D, Zhang L, Rebar E J, Gregory P D, Urnov F D, Jacob H J, Buelow R.2009. Knockout Ratsvia Embryo Microinjection of Zinc-Finger Nucleases. Science,325(5939):433.
Giot L, Bader J S, Brouwer C, Chaudhuri A, Kuang B, Li Y, Hao Y L, Ooi C E, Godwin B, Vitols E,Vijayadamodar G, Pochart P, Machineni H, Welsh M, Kong Y, Zerhusen B, Malcolm R, Varrone Z, CollisA, Minto M, Burgess S, McDaniel L, Stimpson E, Spriggs F, Williams J, Neurath K, Ioime N, Agee M,Voss E, Furtak K, Renzulli R, Aanensen N, Carrolla S, Bickelhaupt E, Lazovatsky Y, DaSilva A, Zhong J,Stanyon C A, Finley R L, White K P, Braverman M, Jarvie T, Gold S, Leach M, Knight J, Shimkets R A,McKenna M P, Chant J, Rothberg J M.2003. A Protein Interaction Map of Drosophila melanogaster.Science,302(5651):1727-1736.
Goldberg A D, Banaszynski L A, Noh K-M, Lewis P W, Elsaesser S J, Stadler S, Dewell S, Law M, Guo X, Li X,Wen D, Chapgier A, DeKelver R C, Miller J C, Lee Y-L, Boydston E A, Holmes M C, Gregory P D,Greally J M, Rafii S, Yang C, Scambler P J, Garrick D, Gibbons R J, Higgs D R, Cristea I M, Urnov F D,Zheng D, Allis C D.2010. Distinct Factors Control Histone Variant H3.3Localization at SpecificGenomic Regions. Cell,140(5):678-691.
Gregory P, Reik A, Zhou Y Y, Hamlett A, Wagner J, Mendel M, Liu P Q, Lee G, Paschon D, Ando D, DiGiusto D,Holmes M, Jensen M.2008. Zinc finger nucleases targeting the glucocorticoid receptor allow IL-13zetakine transgenic CTLs to kill glioblastoma cells in vivo in the presence of immunosuppressiveglucocorticoids. Human Gene Therapy,19(10):1084-1084.
Guo J, Gaj T, Barbas Iii C F.2010. Directed Evolution of an Enhanced and Highly Efficient FokⅠ CleavageDomain for Zinc Finger Nucleases. Journal of Molecular Biology,400(1):96-107.
Gupta A, Christensen R G, Rayla A L, Lakshmanan A, Stormo G D, Wolfe S A.2012. An optimized two-fingerarchive for ZFN-mediated gene targeting. Nat Meth,9(6):588-590.
Hall T M T.2005. Multiple modes of RNA recognition by zinc finger proteins. Current Opinion in StructuralBiology,15(3):367-373.
Handel E M, Cathomen T.2011. Zinc-Finger Nuclease Based Genome Surgery: It's All About Specificity.Current Gene Therapy,11(1):28-37.
Hauschild-Quintern J, Petersen B, Queisser A-L, Lucas-Hahn A, Schwinzer R, Niemann H.2013. Gendernon-specific efficacy of ZFN mediated gene targeting in pigs. Transgenic Research,22(1):1-3.
Hauschild J, Petersen B, Santiago Y, Queisser A-L, Carnwath J W, Lucas-Hahn A, Zhang L, Meng X, Gregory PD, Schwinzer R, Cost G J, Niemann H.2011. Efficient generation of a biallelic knockout in pigs usingzinc-finger nucleases. Proceedings of the National Academy of Sciences,108(29):12013-12017.
Helleday T.2003. Pathways for mitotic homologous recombination in mammalian cells. MutationResearch/Fundamental and Molecular Mechanisms of Mutagenesis,532(1–2):103-115.
Herrmann F, Garriga-Canut M, Baumstark R, Fajardo-Sanchez E, Cotterell J, Minoche A, Himmelbauer H,Isalan M.2011. p53Gene Repair with Zinc Finger Nucleases Optimised by Yeast1-Hybrid and Validatedby Solexa Sequencing. PLoS ONE,6(6): e20913.
Hockemeyer D, Soldner F, Beard C, Gao Q, Mitalipova M, DeKelver R C, Katibah G E, Amora R, Boydston EA, Zeitler B, Meng X, Miller J C, Zhang L, Rebar E J, Gregory P D, Urnov F D, Jaenisch R.2009.Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases.Nat Biotech,27(9):851-857.
Holt N, Wang J, Kim K, Friedman G, Wang X, Taupin V, Crooks G M, Kohn D B, Gregory P D, Holmes M C,Cannon P M.2010. Human hematopoietic stem/progenitor cells modified by zinc-finger nucleasestargeted to CCR5control HIV-1in vivo. Nat Biotech,28(8):839-847.
Hubsman M, Yudkovsky G, Aronheim A.2001. A novel approach for the identification of protein–proteininteraction with integral membrane proteins. Nucleic Acids Research,29(4): e18-e18.
Hurt J A, Thibodeau S A, Hirsh A S, Pabo C O, Joung J K.2003. Highly specific zinc finger proteins obtained bydirected domain shuffling and cell-based selection. Proceedings of the National Academy of Sciences,100(21):12271-12276.
Jamieson A C, Kim S-H, Wells J A.1994. In vitro selection of zinc fingers with altered DNA-binding specificity.Biochemistry,33(19):5689-5695.
Jandal J M.1996. Comparative aspects of goat and sheep milk. Small Ruminant Research,22(2):177-185.
Jayakanthan M, Muthukumaran J, Chandrasekar S, Chawla K, Punetha A, Sundar D.2009. ZifBASE: a databaseof zinc finger proteins and associated resources. BMC Genomics,10(1):421.
Johnsson N, Varshavsky A.1994. Split ubiquitin as a sensor of protein interactions in vivo. Proceedings of theNational Academy of Sciences,91(22):10340.
Kim H, Kim M-S, Wee G, Lee C-i, Kim H, Kim J-S.2013. Magnetic Separation and Antibiotics SelectionEnable Enrichment of Cells with ZFN/TALEN-Induced Mutations. PLoS ONE,8(2): e56476.
Kim H, Um E, Cho S-R, Jung C, Kim H, Kim J-S.2011. Surrogate reporters for enrichment of cells withnuclease-induced mutations. Nat Meth,8(11):941-943.
Kim H J, Lee H J, Kim H, Cho S W, Kim J-S.2009. Targeted genome editing in human cells with zinc fingernucleases constructed via modular assembly. Genome Research,19(7):1279-1288.
Kim Y G, Cha J, Chandrasegaran S.1996. Hybrid restriction enzymes: zinc finger fusions to Fok I cleavagedomain. Proceedings of the National Academy of Sciences,93(3):1156-1160.
Klug A.1999. Zinc finger peptides for the regulation of gene expression. Journal of Molecular Biology,293(2):215-218.
Klug A.2010. The Discovery of Zinc Fingers and Their Applications in Gene Regulation and GenomeManipulation. Annual Review of Biochemistry,79(1):213-231.
Klug A, Rhodes D.1987. Zinc Fingers: A Novel Protein Fold for Nucleic Acid Recognition. Cold Spring HarborSymposia on Quantitative Biology,52(473-482.
Lee H J, Kim E, Kim J S.2010. Targeted chromosomal deletions in human cells using zinc finger nucleases.Genome Research,20(1):81-89.
Li P, Estrada J L, Burlak C, Tector A J.2013. Biallelic knockout of the α-1,3galactosyltransferase gene inporcine liver-derived cells using zinc finger nucleases. Journal of Surgical Research,181(1): e39-e45.
Li S, Armstrong C M, Bertin N, Ge H, Milstein S, Boxem M, Vidalain P-O, Han J-D J, Chesneau A, Hao T,Goldberg D S, Li N, Martinez M, Rual J-F, Lamesch P, Xu L, Tewari M, Wong S L, Zhang L V, Berriz GF, Jacotot L, Vaglio P, Reboul J, Hirozane-Kishikawa T, Li Q, Gabel H W, Elewa A, Baumgartner B, RoseD J, Yu H, Bosak S, Sequerra R, Fraser A, Mango S E, Saxton W M, Strome S, van den Heuvel S, Piano F,Vandenhaute J, Sardet C, Gerstein M, Doucette-Stamm L, Gunsalus K C, Harper J W, Cusick M E, RothF P, Hill D E, Vidal M.2004. A Map of the Interactome Network of the Metazoan C. elegans. Science,303(5657):540-543.
Liu P-Q, Chan E M, Cost G J, Zhang L, Wang J, Miller J C, Guschin D Y, Reik A, Holmes M C, Mott J E,Collingwood T N, Gregory P D.2010. Generation of a triple-gene knockout mammalian cell line usingengineered zinc-finger nucleases. Biotechnology and Bioengineering,106(1):97-105.
Liu Q, Xia Z, Case C C.2002. Validated Zinc Finger Protein Designs for All16GNN DNA Triplet Targets.Journal of Biological Chemistry,277(6):3850-3856.
Lombardo A, Genovese P, Beausejour C M, Colleoni S, Lee Y-L, Kim K A, Ando D, Urnov F D, Galli C,Gregory P D, Holmes M C, Naldini L.2007. Gene editing in human stem cells using zinc finger nucleasesand integrase-defective lentiviral vector delivery. Nat Biotech,25(11):1298-1306.
Lusser M, Parisi C, Plan D, Rodriguez-Cerezo E.2012. Deployment of new biotechnologies in plant breeding.Nat Biotech,30(3):231-239.
Ménoret S, Iscache A-L, Tesson L, Rémy S, Usal C, Osborn M J, Cost G J, Brüggemann M, Buelow R, Anegon I.2010. Characterization of immunoglobulin heavy chain knockout rats. European Journal of Immunology,40(10):2932-2941.
Maeder M L, Thibodeau-Beganny S, Osiak A, Wright D A, Anthony R M, Eichtinger M, Jiang T, Foley J E,Winfrey R J, Townsend J A, Unger-Wallace E, Sander J D, Müller-Lerch F, Fu F, Pearlberg J, G bel C,Dassie Justin P, Pruett-Miller S M, Porteus M H, Sgroi D C, Iafrate A J, Dobbs D, McCray P B, CathomenT, Voytas D F, Joung J K.2008. Rapid Open-Source Engineering of Customized Zinc-FingerNucleases for Highly Efficient Gene Modification. Molecular cell,31(2):294-301.
Maeder M L, Thibodeau-Beganny S, Sander J D, Voytas D F, Joung J K.2009. Oligomerized pool engineering(OPEN): an 'open-source' protocol for making customized zinc-finger arrays. Nat. Protocols,4(10):1471-1501.
Maga E A, Daftari P, Kültz D, Penedo M C T.2009. Prevalence of αs1-casein genotypes in American dairy goats.Journal of Animal Science,87(11):3464-3469.
Mashimo T, Takizawa A, Voigt B, Yoshimi K, Hiai H, Kuramoto T, Serikawa T.2010. Generation of KnockoutRats with X-Linked Severe Combined Immunodeficiency (X-SCID) Using Zinc-Finger Nucleases. PLoSONE,5(1): e8870.
Meng X, Noyes M B, Zhu L J, Lawson N D, Wolfe S A.2008. Targeted gene inactivation in zebrafish usingengineered zinc-finger nucleases. Nat Biotech,26(6):695-701.
Mestawet T A, Girma A, dn y T, Devold T G, Vegarud G E. Newly identified mutations at the CSN1S1gene inEthiopian goats affect casein content and coagulation properties of their milk. Journal of Dairy Science,0).
Miller J, McLachlan A, Klug A.1985. Repetitive zinc-binding domains in the protein transcription factor IIIAfrom Xenopus oocytes. The EMBO journal,4(6):1609.
Miller J C, Holmes M C, Wang J, Guschin D Y, Lee Y-L, Rupniewski I, Beausejour C M, Waite A J, Wang N S,Kim K A, Gregory P D, Pabo C O, Rebar E J.2007. An improved zinc-finger nuclease architecture forhighly specific genome editing. Nat Biotech,25(7):778-785.
Mockli N, Deplazes A, Hassa P O, Zhang Z, Peter M, Hottiger M O, Stagljar I, Auerbach D.2007. Yeastsplit-ubiquitin-based cytosolic screening system to detect interactions between transcriptionally activeproteins. BioTechniques,42(6):725.
Moehle E A, Rock J M, Lee Y-L, Jouvenot Y, DeKelver R C, Gregory P D, Urnov F D, Holmes M C.2007.Targeted gene addition into a specified location in the human genome using designed zinc fingernucleases. Proceedings of the National Academy of Sciences,104(9):3055-3060.
Monaci L, Tregoat V, van Hengel A J, Anklam E.2006. Milk allergens, their characteristics and their detection infood: A review. European Food Research and Technology,223(2):149-179.
Moore M, Ullman C.2003. Recent developments in the engineering of zinc finger proteins. Briefings inFunctional Genomics&Proteomics,1(4):342-355.
Moreno C, Hoffman M, Stodola T J, Didier D N, Lazar J, Geurts A M, North P E, Jacob H J, Greene A S.2011.Creation and Characterization of a Renin Knockout Rat. Hypertension,57(3):614-619.
Morton J, Davis M W, Jorgensen E M, Carroll D.2006. Induction and repair of zinc-finger nuclease-targeteddouble-strand breaks in Caenorhabditis elegans somatic cells. Proceedings of the National Academy ofSciences,103(44):16370-16375.
Nassif N, Penney J, Pal S, Engels W R, Gloor G B.1994. Efficient copying of nonhomologous sequences fromectopic sites via P-element-induced gap repair. Molecular and Cellular Biology,14(3):1613-1625.
Novembre J, Galvani A P, Slatkin M.2005. The Geographic Spread of the CCR5Δ32HIV-Resistance Allele.PLoS Biol,3(11): e339.
Noyes M B, Meng X, Wakabayashi A, Sinha S, Brodsky M H, Wolfe S A.2008. A systematic characterization offactors that regulate Drosophila segmentation via a bacterial one-hybrid system. Nucleic Acids Research,36(8):2547-2560.
Osakabe K, Osakabe Y, Toki S.2010. Site-directed mutagenesis in Arabidopsis using custom-designed zincfinger nucleases. Proceedings of the National Academy of Sciences,107(26):12034-12039.
Perez-Pinera P, Ousterout D G, Brown M T, Gersbach C A.2012. Gene targeting to the ROSA26locus directedby engineered zinc finger nucleases. Nucleic Acids Research,40(8):3741-3752.
Perez E E, Wang J, Miller J C, Jouvenot Y, Kim K A, Liu O, Wang N, Lee G, Bartsevich V V, Lee Y-L, GuschinD Y, Rupniewski I, Waite A J, Carpenito C, Carroll R G, S Orange J, Urnov F D, Rebar E J, Ando D,Gregory P D, Riley J L, Holmes M C, June C H.2008. Establishment of HIV-1resistance in CD4+T cellsby genome editing using zinc-finger nucleases. Nat Biotech,26(7):808-816.
Pirisi A, Colin O, Laurent F, Scher J, Parmentier M.1994. Comparison of milk composition, cheesemakingproperties and textural characteristics of the cheese from two groups of goats with a high or low rate ofαS1-casein synthesis. International Dairy Journal,4(4):329-345.
Plessis A, Perrin A, Haber J E, Dujon B.1992. Site-specific recombination determined by I-SceI, amitochondrial group I intron-encoded endonuclease expressed in the yeast nucleus. Genetics,130(3):451-460.
Porteus M.2007. Using homologous recombination to manipulate the genome of human somatic cells.Biotechnology and Genetic Engineering Reviews,24(1):195-212.
Porteus M H, Baltimore D.2003. Chimeric Nucleases Stimulate Gene Targeting in Human Cells. Science,300(5620):763.
Rémy S, Tesson L, Ménoret S, Usal C, Scharenberg A, Anegon I.2010. Zinc-finger nucleases: a powerful toolfor genetic engineering of animals. Transgenic Research,19(3):363-371.
Ramalingam S, Kandavelou K, Rajenderan R, Chandrasegaran S.2011. Creating Designed Zinc-FingerNucleases with Minimal Cytotoxicity. Journal of Molecular Biology,405(3):630-641.
Ramirez C L, Foley J E, Wright D A, Muller-Lerch F, Rahman S H, Cornu T I, Winfrey R J, Sander J D, Fu F,Townsend J A, Cathomen T, Voytas D F, Joung J K.2008. Unexpected failure rates for modular assemblyof engineered zinc fingers. Nat Meth,5(5):374-375.
Rebar E, Pabo C.1994. Zinc finger phage: affinity selection of fingers with new DNA-binding specificities.Science,263(5147):671-673.
Reynolds L, Ullman C, Moore M, Isalan M, West M J, Clapham P, Klug A, Choo Y.2003. Repression of theHIV-15′LTR promoter and inhibition of HIV-1replication by using engineered zinc-fingertranscription factors. Proceedings of the National Academy of Sciences,100(4):1615-1620.
Ross J, Whyte J, Zhao J, Samuel M, Wells K, Prather R.2010. Optimization of square-wave electroporation fortransfection of porcine fetal fibroblasts. Transgenic Research,19(4):611-620.
Samson M, Libert F, Doranz B J, Rucker J, Liesnard C, Farber C-M, Saragosti S, Lapoumeroulie C, Cognaux J,Forceille C, Muyldermans G, Verhofstede C, Burtonboy G, Georges M, Imai T, Rana S, Yi Y, Smyth R J,Collman R G, Doms R W, Vassart G, Parmentier M.1996. Resistance to HIV-1infection in Caucasianindividuals bearing mutant alleles of the CCR-5chemokine receptor gene. Nature,382(6593):722-725.
Sander J D, Dahlborg E J, Goodwin M J, Cade L, Zhang F, Cifuentes D, Curtin S J, Blackburn J S,Thibodeau-Beganny S, Qi Y, Pierick C J, Hoffman E, Maeder M L, Khayter C, Reyon D, Dobbs D,Langenau D M, Stupar R M, Giraldez A J, Voytas D F, Peterson R T, Yeh J-R J, Joung J K.2011.Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA). Nat Meth,8(1):67-69.
Sander J D, Zaback P, Joung J K, Voytas D F, Dobbs D.2009. An affinity-based scoring scheme for predictingDNA-binding activities of modularly assembled zinc-finger proteins. Nucleic Acids Research,37(2):506-515.
Santiago Y, Chan E, Liu P-Q, Orlando S, Zhang L, Urnov F D, Holmes M C, Guschin D, Waite A, Miller J C,Rebar E J, Gregory P D, Klug A, Collingwood T N.2008. Targeted gene knockout in mammalian cells byusing engineered zinc-finger nucleases. Proceedings of the National Academy of Sciences,105(15):5809-5814.
Segal D J, Beerli R R, Blancafort P, Dreier B, Effertz K, Huber A, Koksch B, Lund C V, Magnenat L, Valente D,Barbas C F.2003. Evaluation of a Modular Strategy for the Construction of Novel Polydactyl Zinc FingerDNA-Binding Proteins. Biochemistry,42(7):2137-2148.
Segal D J, Dreier B, Beerli R R, Barbas C F.1999. Toward controlling gene expression at will: Selection anddesign of zinc finger domains recognizing each of the5′-GNN-3′DNA target sequences. Proceedingsof the National Academy of Sciences,96(6):2758-2763.
Shieh J-C2010. Bipartite Selection of Zinc Fingers by Phage Display for Any9-bp DNA Target Site#[M], TEngineered Zinc Finger Proteins:51-76.
Shukla V K, Doyon Y, Miller J C, DeKelver R C, Moehle E A, Worden S E, Mitchell J C, Arnold N L, GopalanS, Meng X, Choi V M, Rock J M, Wu Y-Y, Katibah G E, Zhifang G, McCaskill D, Simpson M A,Blakeslee B, Greenwalt S A, Butler H J, Hinkley S J, Zhang L, Rebar E J, Gregory P D, Urnov F D.2009.Precise genome modification in the crop species Zea mays using zinc-finger nucleases. Nature,459(7245):437-441.
Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck F H, Goehler H, Stroedicke M, Zenkner M, Schoenherr A,Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toks z E, Droege A,Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker E E.2005. A Human Protein-Protein InteractionNetwork: A Resource for Annotating the Proteome. Cell,122(6):957-968.
Szczepek M, Brondani V, Buchel J, Serrano L, Segal D J, Cathomen T.2007. Structure-based redesign of thedimerization interface reduces the toxicity of zinc-finger nucleases. Nat Biotech,25(7):786-793.
Takasu Y, Kobayashi I, Beumer K, Uchino K, Sezutsu H, Sajwan S, Carroll D, Tamura T, Zurovec M.2010.Targeted mutagenesis in the silkworm Bombyx mori using zinc finger nuclease mRNA injection. InsectBiochemistry and Molecular Biology,40(10):759-765.
Thomas K R, Folger K R, Capecchi M R.1986. High frequency targeting of genes to specific sites in themammalian genome. Cell,44(3):419-428.
Townsend J A, Wright D A, Winfrey R J, Fu F, Maeder M L, Joung J K, Voytas D F.2009. High-frequencymodification of plant genes using engineered zinc-finger nucleases. Nature,459(7245):442-445.
Uetz P, Giot L, Cagney G, Mansfield T A, Judson R S, Knight J R, Lockshon D, Narayan V, Srinivasan M,Pochart P, Qureshi-Emili A, Li Y, Godwin B, Conover D, Kalbfleisch T, Vijayadamodar G, Yang M,Johnston M, Fields S, Rothberg J M.2000. A comprehensive analysis of protein-protein interactions inSaccharomyces cerevisiae. Nature,403(6770):623-627.
Urnov F D, Miller J C, Lee Y-L, Beausejour C M, Rock J M, Augustus S, Jamieson A C, Porteus M H, Gregory PD, Holmes M C.2005. Highly efficient endogenous human gene correction using designed zinc-fingernucleases. Nature,435(7042):646-651.
Urnov F D, Rebar E J, Holmes M C, Zhang H S, Gregory P D.2010. Genome editing with engineered zincfinger nucleases. Nat Rev Genet,11(9):636-646.
Voytas D F.2013. Plant Genome Engineering with Sequence-Specific Nucleases. Annual Review of PlantBiology,64(1):327-350.
Watanabe M, Umeyama K, Matsunari H, Takayanagi S, Haruyama E, Nakano K, Fujiwara T, Ikezawa Y,Nakauchi H, Nagashima H.2010. Knockout of exogenous EGFP gene in porcine somatic cells usingzinc-finger nucleases. Biochemical and Biophysical Research Communications,402(1):14-18.
Wolfe S A, Greisman H A, Ramm E I, Pabo C O.1999. Analysis of zinc fingers optimized via phage display:evaluating the utility of a recognition code. Journal of Molecular Biology,285(5):1917-1934.
Wright D A, Thibodeau-Beganny S, Sander J D, Winfrey R J, Hirsh A S, Eichtinger M, Fu F, Porteus M H,Dobbs D, Voytas D F, Joung J K.2006. Standardized reagents and protocols for engineering zinc fingernucleases by modular assembly. Nat. Protocols,1(4):1637-1652.
Xiong K, Li S, Zhang H, Cui Y, Yu D, Li Y, Sun W, Fu Y, Teng Y, Liu Z, Zhou X, Xiao P, Li J, Liu H, Chen J.2013. Targeted editing of goat genome with modular-assembly zinc finger nucleases based on activityprediction by computational molecular modeling. Molecular Biology Reports,40(7):4251-4256.
Yu S, Luo J, Song Z, Ding F, Dai Y, Li N.2011. Highly efficient modification of beta-lactoglobulin (BLG) genevia zinc-finger nucleases in cattle. Cell Res,21(11):1638-1640.
Zhang F, Maeder M L, Unger-Wallace E, Hoshaw J P, Reyon D, Christian M, Li X, Pierick C J, Dobbs D,Peterson T, Joung J K, Voytas D F.2010. High frequency targeted mutagenesis in Arabidopsis thalianausing zinc finger nucleases. Proceedings of the National Academy of Sciences,107(26):12028-12033.
Zheng H, Wilson J H.1990. Gene targeting in normal and amplified cell lines. Nature,344(6262):170-173.
Zou J, Maeder M L, Mali P, Pruett-Miller S M, Thibodeau-Beganny S, Chou B-K, Chen G, Ye Z, Park I-H,Daley G Q, Porteus M H, Joung J K, Cheng L.2009. Gene Targeting of a Disease-Related Gene inHuman Induced Pluripotent Stem and Embryonic Stem Cells. Cell Stem Cell,5(1):97-110.
Aronheim A, Zandi E, Hennemann H, Elledge S J, Karin M.1997. Isolation of an AP-1repressor by a novelmethod for detecting protein-protein interactions. Molecular and cellular biology,17(6):3094-3102.
Bae K-H, Do Kwon Y, Shin H-C, Hwang M-S, Ryu E-H, Park K-S, Yang H-Y, Lee D-k, Lee Y, Park J, SunKwon H, Kim H-W, Yeh B-I, Lee H-W, Hyung Sohn S, Yoon J, Seol W, Kim J-S.2003. Human zincfingers as building blocks in the construction of artificial transcription factors. Nat Biotech,21(3):275-280.
Bedell V M, Wang Y, Campbell J M, Poshusta T L, Starker C G, Krug Ii R G, Tan W, Penheiter S G, Ma A C,Leung A Y H, Fahrenkrug S C, Carlson D F, Voytas D F, Clark K J, Essner J J, Ekker S C.2012. In vivogenome editing using a high-efficiency TALEN system. Nature,491(7422):114-118.
Bellaiche Y, Mogila V, Perrimon N.1999. I-SceI Endonuclease, a New Tool for Studying DNA Double-StrandBreak Repair Mechanisms in Drosophila. Genetics,152(3):1037-1044.
Benabdallah B F, Allard E, Yao S, Friedman G, Gregory P D, Eliopoulos N, Fradette J, Spees J L, Haddad E,Holmes M C, Beausejour C M.2010. Targeted gene addition to human mesenchymal stromal cells as acell-based plasma-soluble protein delivery platform. Cytotherapy,12(3):394-399.
Beumer K, Bhattacharyya G, Bibikova M, Trautman J K, Carroll D.2006. Efficient Gene Targeting inDrosophila With Zinc-Finger Nucleases. Genetics,172(4):2391-2403.
Beumer K J, Trautman J K, Bozas A, Liu J-L, Rutter J, Gall J G, Carroll D.2008. Efficient gene targeting inDrosophila by direct embryo injection with zinc-finger nucleases. Proceedings of the National Academyof Sciences,105(50):19821-19826.
Bibikova M, Beumer K, Trautman J K, Carroll D.2003. Enhancing Gene Targeting with Designed Zinc FingerNucleases. Science,300(5620):764.
Bibikova M, Carroll D, Segal D J, Trautman J K, Smith J, Kim Y-G, Chandrasegaran S.2001. Stimulation ofHomologous Recombination through Targeted Cleavage by Chimeric Nucleases. Molecular and CellularBiology,21(1):289-297.
Bibikova M, Golic M, Golic K G, Carroll D.2002. Targeted Chromosomal Cleavage and Mutagenesis inDrosophila Using Zinc-Finger Nucleases. Genetics,161(3):1169-1175.
Bitinaite J, Wah D A, Aggarwal A K, Schildkraut I.1998. FokⅠ dimerization is required for DNA cleavage.Proceedings of the National Academy of Sciences,95(18):10570-10575.
Bot A.2010. The Landmark Approval of Provenge (R), What It Means to Immunology and "In This Issue": TheComplex Relation Between Vaccines and Autoimmunity. International Reviews of Immunology,29(3):235-238.
Bozas A, Beumer K J, Trautman J K, Carroll D.2009. Genetic Analysis of Zinc-Finger Nuclease-Induced GeneTargeting in Drosophila. Genetics,182(3):641-651.
Brown R S.2005. Zinc finger proteins: getting a grip on RNA. Current Opinion in Structural Biology,15(1):94-98.
Brunet E, Simsek D, Tomishima M, DeKelver R, Choi V M, Gregory P, Urnov F, Weinstock D M, Jasin M.2009.Chromosomal translocations induced at specified loci in human stem cells. Proceedings of the NationalAcademy of Sciences,106(26):10620-10625.
Cai C, Doyon Y, Ainley W M, Miller J, DeKelver R, Moehle E, Rock J, Lee Y-L, Garrison R, Schulenberg L,Blue R, Worden A, Baker L, Faraji F, Zhang L, Holmes M, Rebar E, Collingwood T, Rubin-Wilson B,Gregory P, Urnov F, Petolino J.2009. Targeted transgene integration in plant cells using designed zincfinger nucleases. Plant Molecular Biology,69(6):699-709.
Cannon P, June C.2011. Chemokine receptor5knockout strategies. Current Opinion in HIV and AIDS,6(1):74-7910.1097/COH.1090b1013e32834122d32834127.
Carroll D.2011. Genome Engineering With Zinc-Finger Nucleases. Genetics,188(4):773-782.
Cebo C, Lopez C, Henry C, Beauvallet C, Ménard O, Bevilacqua C, Bouvier F, Caillat H, Martin P.2012. Goatαs1-casein genotype affects milk fat globule physicochemical properties and the composition of the milkfat globule membrane. Journal of Dairy Science,95(11):6215-6229.
Cermak T, Doyle E L, Christian M, Wang L, Zhang Y, Schmidt C, Baller J A, Somia N V, Bogdanove A J, VoytasD F.2011. Efficient design and assembly of custom TALEN and other TAL effector-based constructs forDNA targeting. Nucleic Acids Research,39(12): e82.
Choo Y, Isalan M.2000. Advances in zinc finger engineering. Current Opinion in Structural Biology,10(4):411-416.
Choo Y, Sanchez-Garcia I, Klug A.1994. In vivo repression by a site-specific DNA-binding protein designedagainst an oncogenic sequence. Nature,372(6507):642-645.
Choulika A, Perrin A, Dujon B, Nicolas J F.1995. Induction of homologous recombination in mammalianchromosomes by using the I-SceI system of Saccharomyces cerevisiae. Molecular and Cellular Biology,15(4):1968-1973.
Christy B, Nathans D.1989. DNA binding site of the growth factor-inducible protein Zif268. Proceedings of theNational Academy of Sciences,86(22):8737-8741.
Clark S, Sherbon J W.2000. Alphas1-casein, milk composition and coagulation properties of goat milk. SmallRuminant Research,38(2):123-134.
Cost G J, Freyvert Y, Vafiadis A, Santiago Y, Miller J C, Rebar E, Collingwood T N, Snowden A, Gregory P D.2010. BAK and BAX deletion using zinc-finger nucleases yields apoptosis-resistant CHO cells.Biotechnology and Bioengineering,105(2):330-340.
Curtin S J, Zhang F, Sander J D, Haun W J, Starker C, Baltes N J, Reyon D, Dahlborg E J, Goodwin M J,Coffman A P, Dobbs D, Joung J K, Voytas D F, Stupar R M.2011. Targeted Mutagenesis of DuplicatedGenes in Soybean with Zinc-Finger Nucleases. Plant Physiology,156(2):466-473.
DeKelver R C, Choi V M, Moehle E A, Paschon D E, Hockemeyer D, Meijsing S H, Sancak Y, Cui X X, SteineE L J, Miller J C, Tam P, Bartsevich V V, Meng X D, Rupniewski I, Gopalan S M, Sun H C, Pitz K J,Rock J M, Zhang L, Davis G D, Rebar E J, Cheeseman I M, Yamamoto K R, Sabatini D M, Jaenisch R,Gregory P D, Urnov F D.2010. Functional genomics, proteomics, and regulatory DNA analysis inisogenic settings using zinc finger nuclease-driven transgenesis into a safe harbor locus in the humangenome. Genome Research,20(8):1133-1142.
Dhanasekaran M, Negi S, Sugiura Y.2005. Designer Zinc Finger Proteins: Tools for Creating ArtificialDNA-Binding Functional Proteins. Accounts of Chemical Research,39(1):45-52.
Dirnberger D, Messerschmid M, Baumeister R.2008. An optimized split-ubiquitin cDNA-library screeningsystem to identify novel interactors of the human Frizzled1receptor. Nucleic Acids Research,36(6): e37.
Doyon Y, McCammon J M, Miller J C, Faraji F, Ngo C, Katibah G E, Amora R, Hocking T D, Zhang L, Rebar EJ, Gregory P D, Urnov F D, Amacher S L.2008. Heritable targeted gene disruption in zebrafish usingdesigned zinc-finger nucleases. Nat Biotech,26(6):702-708.
Doyon Y, Vo T D, Mendel M C, Greenberg S G, Wang J, Xia D F, Miller J C, Urnov F D, Gregory P D, HolmesM C.2011. Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures.Nat Meth,8(1):74-79.
Dreier B, Beerli R R, Segal D J, Flippin J D, Barbas C F.2001. Development of Zinc Finger Domains forRecognition of the5′-ANN-3′Family of DNA Sequences and Their Use in the Construction ofArtificial Transcription Factors. Journal of Biological Chemistry,276(31):29466-29478.
Dreier B, Fuller R P, Segal D J, Lund C V, Blancafort P, Huber A, Koksch B, Barbas C F.2005. Development ofZinc Finger Domains for Recognition of the5′-CNN-3′Family DNA Sequences and Their Use in theConstruction of Artificial Transcription Factors. Journal of Biological Chemistry,280(42):35588-35597.
Drury L1994. Transformation of Bacteria by Electroporation [M]//A. HARWOOD, Protocols for Gene Analysis.Humana Press:1-8.
Durai S, Mani M, Kandavelou K, Wu J, Porteus M H, Chandrasegaran S.2005. Zinc finger nucleases:custom-designed molecular scissors for genome engineering of plant and mammalian cells. Nucleic AcidsResearch,33(18):5978-5990.
Elrod-Erickson M, Rould M A, Nekludova L, Pabo C O.1996. Zif268protein-DNA complex refined at1.6A: amodel system for understanding zinc finger-DNA interactions. Structure (London, England:1993),4(10):1171-1180.
Epinat J C, Arnould S, Chames P, Rochaix P, Desfontaines D, Puzin C, Patin A, Zanghellini A, Paques F, LacroixE.2003. A novel engineered meganuclease induces homologous recombination in yeast and mammaliancells. Nucleic Acids Research,31(11):2952-2962.
Farrell Jr H M, Jimenez-Flores R, Bleck G T, Brown E M, Butler J E, Creamer L K, Hicks C L, Hollar C M,Ng-Kwai-Hang K F, Swaisgood H E.2004. Nomenclature of the Proteins of Cows’ Milk—Sixth Revision.Journal of Dairy Science,87(6):1641-1674.
Feligini M, Frati S, Curik V C, Brambilla A, Parma P, Curik I, Greppi G F, Enne G.2005. Caprine as1-caseinpolymorphism: characterisation of A, B, E and F variants by means of various biochemical and moleculartechniques. Food Technol. Biotechnol,43(123-132.
Fields S, Song O-k.1989. A novel genetic system to detect protein–protein interactions. Nature,340(6230):245-246.
Finn R D, Tate J, Mistry J, Coggill P C, Sammut S J, Hotz H-R, Ceric G, Forslund K, Eddy S R, Sonnhammer EL L, Bateman A.2008. The Pfam protein families database. Nucleic Acids Research,36(suppl1):D281-D288.
Formosa T, Alberts B M.1986. DNA synthesis dependent on genetic recombination: Characterization of areaction catalyzed by purified bacteriophage T4proteins. Cell,47(5):793-806.
Fu F, Sander J D, Maeder M, Thibodeau-Beganny S, Joung J K, Dobbs D, Miller L, Voytas D F.2009. ZincFinger Database (ZiFDB): a repository for information on C2H2zinc fingers and engineered zinc-fingerarrays. Nucleic Acids Research,37(suppl1): D279-D283.
Gaj T, Gersbach C A, Barbas Iii C F.2013. ZFN, TALEN, and CRISPR/Cas-based methods for genomeengineering. Trends in Biotechnology,31(7):397-405.
Galli C, Perota A, Brunetti D, Lagutina I, Lazzari G, Lucchini F.2010. Genetic engineering includingsuperseding microinjection: new ways to make GM pigs. Xenotransplantation,17(6):397-410.
Gamsjaeger R, Liew C K, Loughlin F E, Crossley M, Mackay J P.2007. Sticky fingers: zinc-fingers asprotein-recognition motifs. Trends in biochemical sciences,32(2):63-70.
Geurts A M, Cost G J, Freyvert Y, Zeitler B, Miller J C, Choi V M, Jenkins S S, Wood A, Cui X, Meng X,Vincent A, Lam S, Michalkiewicz M, Schilling R, Foeckler J, Kalloway S, Weiler H, Ménoret S, AnegonI, Davis G D, Zhang L, Rebar E J, Gregory P D, Urnov F D, Jacob H J, Buelow R.2009. Knockout Ratsvia Embryo Microinjection of Zinc-Finger Nucleases. Science,325(5939):433.
Giot L, Bader J S, Brouwer C, Chaudhuri A, Kuang B, Li Y, Hao Y L, Ooi C E, Godwin B, Vitols E,Vijayadamodar G, Pochart P, Machineni H, Welsh M, Kong Y, Zerhusen B, Malcolm R, Varrone Z, CollisA, Minto M, Burgess S, McDaniel L, Stimpson E, Spriggs F, Williams J, Neurath K, Ioime N, Agee M,Voss E, Furtak K, Renzulli R, Aanensen N, Carrolla S, Bickelhaupt E, Lazovatsky Y, DaSilva A, Zhong J,Stanyon C A, Finley R L, White K P, Braverman M, Jarvie T, Gold S, Leach M, Knight J, Shimkets R A,McKenna M P, Chant J, Rothberg J M.2003. A Protein Interaction Map of Drosophila melanogaster.Science,302(5651):1727-1736.
Goldberg A D, Banaszynski L A, Noh K-M, Lewis P W, Elsaesser S J, Stadler S, Dewell S, Law M, Guo X, Li X,Wen D, Chapgier A, DeKelver R C, Miller J C, Lee Y-L, Boydston E A, Holmes M C, Gregory P D,Greally J M, Rafii S, Yang C, Scambler P J, Garrick D, Gibbons R J, Higgs D R, Cristea I M, Urnov F D,Zheng D, Allis C D.2010. Distinct Factors Control Histone Variant H3.3Localization at SpecificGenomic Regions. Cell,140(5):678-691.
Gregory P, Reik A, Zhou Y Y, Hamlett A, Wagner J, Mendel M, Liu P Q, Lee G, Paschon D, Ando D, DiGiusto D,Holmes M, Jensen M.2008. Zinc finger nucleases targeting the glucocorticoid receptor allow IL-13zetakine transgenic CTLs to kill glioblastoma cells in vivo in the presence of immunosuppressiveglucocorticoids. Human Gene Therapy,19(10):1084-1084.
Guo J, Gaj T, Barbas Iii C F.2010. Directed Evolution of an Enhanced and Highly Efficient FokⅠ CleavageDomain for Zinc Finger Nucleases. Journal of Molecular Biology,400(1):96-107.
Gupta A, Christensen R G, Rayla A L, Lakshmanan A, Stormo G D, Wolfe S A.2012. An optimized two-fingerarchive for ZFN-mediated gene targeting. Nat Meth,9(6):588-590.
Hall T M T.2005. Multiple modes of RNA recognition by zinc finger proteins. Current Opinion in StructuralBiology,15(3):367-373.
Handel E M, Cathomen T.2011. Zinc-Finger Nuclease Based Genome Surgery: It's All About Specificity.Current Gene Therapy,11(1):28-37.
Hauschild-Quintern J, Petersen B, Queisser A-L, Lucas-Hahn A, Schwinzer R, Niemann H.2013. Gendernon-specific efficacy of ZFN mediated gene targeting in pigs. Transgenic Research,22(1):1-3.
Hauschild J, Petersen B, Santiago Y, Queisser A-L, Carnwath J W, Lucas-Hahn A, Zhang L, Meng X, Gregory PD, Schwinzer R, Cost G J, Niemann H.2011. Efficient generation of a biallelic knockout in pigs usingzinc-finger nucleases. Proceedings of the National Academy of Sciences,108(29):12013-12017.
Helleday T.2003. Pathways for mitotic homologous recombination in mammalian cells. MutationResearch/Fundamental and Molecular Mechanisms of Mutagenesis,532(1–2):103-115.
Herrmann F, Garriga-Canut M, Baumstark R, Fajardo-Sanchez E, Cotterell J, Minoche A, Himmelbauer H,Isalan M.2011. p53Gene Repair with Zinc Finger Nucleases Optimised by Yeast1-Hybrid and Validatedby Solexa Sequencing. PLoS ONE,6(6): e20913.
Hockemeyer D, Soldner F, Beard C, Gao Q, Mitalipova M, DeKelver R C, Katibah G E, Amora R, Boydston EA, Zeitler B, Meng X, Miller J C, Zhang L, Rebar E J, Gregory P D, Urnov F D, Jaenisch R.2009.Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases.Nat Biotech,27(9):851-857.
Holt N, Wang J, Kim K, Friedman G, Wang X, Taupin V, Crooks G M, Kohn D B, Gregory P D, Holmes M C,Cannon P M.2010. Human hematopoietic stem/progenitor cells modified by zinc-finger nucleasestargeted to CCR5control HIV-1in vivo. Nat Biotech,28(8):839-847.
Hubsman M, Yudkovsky G, Aronheim A.2001. A novel approach for the identification of protein–proteininteraction with integral membrane proteins. Nucleic Acids Research,29(4): e18-e18.
Hurt J A, Thibodeau S A, Hirsh A S, Pabo C O, Joung J K.2003. Highly specific zinc finger proteins obtained bydirected domain shuffling and cell-based selection. Proceedings of the National Academy of Sciences,100(21):12271-12276.
Jamieson A C, Kim S-H, Wells J A.1994. In vitro selection of zinc fingers with altered DNA-binding specificity.Biochemistry,33(19):5689-5695.
Jandal J M.1996. Comparative aspects of goat and sheep milk. Small Ruminant Research,22(2):177-185.
Jayakanthan M, Muthukumaran J, Chandrasekar S, Chawla K, Punetha A, Sundar D.2009. ZifBASE: a databaseof zinc finger proteins and associated resources. BMC Genomics,10(1):421.
Johnsson N, Varshavsky A.1994. Split ubiquitin as a sensor of protein interactions in vivo. Proceedings of theNational Academy of Sciences,91(22):10340.
Kim H, Kim M-S, Wee G, Lee C-i, Kim H, Kim J-S.2013. Magnetic Separation and Antibiotics SelectionEnable Enrichment of Cells with ZFN/TALEN-Induced Mutations. PLoS ONE,8(2): e56476.
Kim H, Um E, Cho S-R, Jung C, Kim H, Kim J-S.2011. Surrogate reporters for enrichment of cells withnuclease-induced mutations. Nat Meth,8(11):941-943.
Kim H J, Lee H J, Kim H, Cho S W, Kim J-S.2009. Targeted genome editing in human cells with zinc fingernucleases constructed via modular assembly. Genome Research,19(7):1279-1288.
Kim Y G, Cha J, Chandrasegaran S.1996. Hybrid restriction enzymes: zinc finger fusions to Fok I cleavagedomain. Proceedings of the National Academy of Sciences,93(3):1156-1160.
Klug A.1999. Zinc finger peptides for the regulation of gene expression. Journal of Molecular Biology,293(2):215-218.
Klug A.2010. The Discovery of Zinc Fingers and Their Applications in Gene Regulation and GenomeManipulation. Annual Review of Biochemistry,79(1):213-231.
Klug A, Rhodes D.1987. Zinc Fingers: A Novel Protein Fold for Nucleic Acid Recognition. Cold Spring HarborSymposia on Quantitative Biology,52(473-482.
Lee H J, Kim E, Kim J S.2010. Targeted chromosomal deletions in human cells using zinc finger nucleases.Genome Research,20(1):81-89.
Li P, Estrada J L, Burlak C, Tector A J.2013. Biallelic knockout of the α-1,3galactosyltransferase gene inporcine liver-derived cells using zinc finger nucleases. Journal of Surgical Research,181(1): e39-e45.
Li S, Armstrong C M, Bertin N, Ge H, Milstein S, Boxem M, Vidalain P-O, Han J-D J, Chesneau A, Hao T,Goldberg D S, Li N, Martinez M, Rual J-F, Lamesch P, Xu L, Tewari M, Wong S L, Zhang L V, Berriz GF, Jacotot L, Vaglio P, Reboul J, Hirozane-Kishikawa T, Li Q, Gabel H W, Elewa A, Baumgartner B, RoseD J, Yu H, Bosak S, Sequerra R, Fraser A, Mango S E, Saxton W M, Strome S, van den Heuvel S, Piano F,Vandenhaute J, Sardet C, Gerstein M, Doucette-Stamm L, Gunsalus K C, Harper J W, Cusick M E, RothF P, Hill D E, Vidal M.2004. A Map of the Interactome Network of the Metazoan C. elegans. Science,303(5657):540-543.
Liu P-Q, Chan E M, Cost G J, Zhang L, Wang J, Miller J C, Guschin D Y, Reik A, Holmes M C, Mott J E,Collingwood T N, Gregory P D.2010. Generation of a triple-gene knockout mammalian cell line usingengineered zinc-finger nucleases. Biotechnology and Bioengineering,106(1):97-105.
Liu Q, Xia Z, Case C C.2002. Validated Zinc Finger Protein Designs for All16GNN DNA Triplet Targets.Journal of Biological Chemistry,277(6):3850-3856.
Lombardo A, Genovese P, Beausejour C M, Colleoni S, Lee Y-L, Kim K A, Ando D, Urnov F D, Galli C,Gregory P D, Holmes M C, Naldini L.2007. Gene editing in human stem cells using zinc finger nucleasesand integrase-defective lentiviral vector delivery. Nat Biotech,25(11):1298-1306.
Lusser M, Parisi C, Plan D, Rodriguez-Cerezo E.2012. Deployment of new biotechnologies in plant breeding.Nat Biotech,30(3):231-239.
Ménoret S, Iscache A-L, Tesson L, Rémy S, Usal C, Osborn M J, Cost G J, Brüggemann M, Buelow R, Anegon I.2010. Characterization of immunoglobulin heavy chain knockout rats. European Journal of Immunology,40(10):2932-2941.
Maeder M L, Thibodeau-Beganny S, Osiak A, Wright D A, Anthony R M, Eichtinger M, Jiang T, Foley J E,Winfrey R J, Townsend J A, Unger-Wallace E, Sander J D, Müller-Lerch F, Fu F, Pearlberg J, G bel C,Dassie Justin P, Pruett-Miller S M, Porteus M H, Sgroi D C, Iafrate A J, Dobbs D, McCray P B, CathomenT, Voytas D F, Joung J K.2008. Rapid Open-Source Engineering of Customized Zinc-FingerNucleases for Highly Efficient Gene Modification. Molecular cell,31(2):294-301.
Maeder M L, Thibodeau-Beganny S, Sander J D, Voytas D F, Joung J K.2009. Oligomerized pool engineering(OPEN): an 'open-source' protocol for making customized zinc-finger arrays. Nat. Protocols,4(10):1471-1501.
Maga E A, Daftari P, Kültz D, Penedo M C T.2009. Prevalence of αs1-casein genotypes in American dairy goats.Journal of Animal Science,87(11):3464-3469.
Mashimo T, Takizawa A, Voigt B, Yoshimi K, Hiai H, Kuramoto T, Serikawa T.2010. Generation of KnockoutRats with X-Linked Severe Combined Immunodeficiency (X-SCID) Using Zinc-Finger Nucleases. PLoSONE,5(1): e8870.
Meng X, Noyes M B, Zhu L J, Lawson N D, Wolfe S A.2008. Targeted gene inactivation in zebrafish usingengineered zinc-finger nucleases. Nat Biotech,26(6):695-701.
Mestawet T A, Girma A, dn y T, Devold T G, Vegarud G E. Newly identified mutations at the CSN1S1gene inEthiopian goats affect casein content and coagulation properties of their milk. Journal of Dairy Science,0).
Miller J, McLachlan A, Klug A.1985. Repetitive zinc-binding domains in the protein transcription factor IIIAfrom Xenopus oocytes. The EMBO journal,4(6):1609.
Miller J C, Holmes M C, Wang J, Guschin D Y, Lee Y-L, Rupniewski I, Beausejour C M, Waite A J, Wang N S,Kim K A, Gregory P D, Pabo C O, Rebar E J.2007. An improved zinc-finger nuclease architecture forhighly specific genome editing. Nat Biotech,25(7):778-785.
Mockli N, Deplazes A, Hassa P O, Zhang Z, Peter M, Hottiger M O, Stagljar I, Auerbach D.2007. Yeastsplit-ubiquitin-based cytosolic screening system to detect interactions between transcriptionally activeproteins. BioTechniques,42(6):725.
Moehle E A, Rock J M, Lee Y-L, Jouvenot Y, DeKelver R C, Gregory P D, Urnov F D, Holmes M C.2007.Targeted gene addition into a specified location in the human genome using designed zinc fingernucleases. Proceedings of the National Academy of Sciences,104(9):3055-3060.
Monaci L, Tregoat V, van Hengel A J, Anklam E.2006. Milk allergens, their characteristics and their detection infood: A review. European Food Research and Technology,223(2):149-179.
Moore M, Ullman C.2003. Recent developments in the engineering of zinc finger proteins. Briefings inFunctional Genomics&Proteomics,1(4):342-355.
Moreno C, Hoffman M, Stodola T J, Didier D N, Lazar J, Geurts A M, North P E, Jacob H J, Greene A S.2011.Creation and Characterization of a Renin Knockout Rat. Hypertension,57(3):614-619.
Morton J, Davis M W, Jorgensen E M, Carroll D.2006. Induction and repair of zinc-finger nuclease-targeteddouble-strand breaks in Caenorhabditis elegans somatic cells. Proceedings of the National Academy ofSciences,103(44):16370-16375.
Nassif N, Penney J, Pal S, Engels W R, Gloor G B.1994. Efficient copying of nonhomologous sequences fromectopic sites via P-element-induced gap repair. Molecular and Cellular Biology,14(3):1613-1625.
Novembre J, Galvani A P, Slatkin M.2005. The Geographic Spread of the CCR5Δ32HIV-Resistance Allele.PLoS Biol,3(11): e339.
Noyes M B, Meng X, Wakabayashi A, Sinha S, Brodsky M H, Wolfe S A.2008. A systematic characterization offactors that regulate Drosophila segmentation via a bacterial one-hybrid system. Nucleic Acids Research,36(8):2547-2560.
Osakabe K, Osakabe Y, Toki S.2010. Site-directed mutagenesis in Arabidopsis using custom-designed zincfinger nucleases. Proceedings of the National Academy of Sciences,107(26):12034-12039.
Perez-Pinera P, Ousterout D G, Brown M T, Gersbach C A.2012. Gene targeting to the ROSA26locus directedby engineered zinc finger nucleases. Nucleic Acids Research,40(8):3741-3752.
Perez E E, Wang J, Miller J C, Jouvenot Y, Kim K A, Liu O, Wang N, Lee G, Bartsevich V V, Lee Y-L, GuschinD Y, Rupniewski I, Waite A J, Carpenito C, Carroll R G, S Orange J, Urnov F D, Rebar E J, Ando D,Gregory P D, Riley J L, Holmes M C, June C H.2008. Establishment of HIV-1resistance in CD4+T cellsby genome editing using zinc-finger nucleases. Nat Biotech,26(7):808-816.
Pirisi A, Colin O, Laurent F, Scher J, Parmentier M.1994. Comparison of milk composition, cheesemakingproperties and textural characteristics of the cheese from two groups of goats with a high or low rate ofαS1-casein synthesis. International Dairy Journal,4(4):329-345.
Plessis A, Perrin A, Haber J E, Dujon B.1992. Site-specific recombination determined by I-SceI, amitochondrial group I intron-encoded endonuclease expressed in the yeast nucleus. Genetics,130(3):451-460.
Porteus M.2007. Using homologous recombination to manipulate the genome of human somatic cells.Biotechnology and Genetic Engineering Reviews,24(1):195-212.
Porteus M H, Baltimore D.2003. Chimeric Nucleases Stimulate Gene Targeting in Human Cells. Science,300(5620):763.
Rémy S, Tesson L, Ménoret S, Usal C, Scharenberg A, Anegon I.2010. Zinc-finger nucleases: a powerful toolfor genetic engineering of animals. Transgenic Research,19(3):363-371.
Ramalingam S, Kandavelou K, Rajenderan R, Chandrasegaran S.2011. Creating Designed Zinc-FingerNucleases with Minimal Cytotoxicity. Journal of Molecular Biology,405(3):630-641.
Ramirez C L, Foley J E, Wright D A, Muller-Lerch F, Rahman S H, Cornu T I, Winfrey R J, Sander J D, Fu F,Townsend J A, Cathomen T, Voytas D F, Joung J K.2008. Unexpected failure rates for modular assemblyof engineered zinc fingers. Nat Meth,5(5):374-375.
Rebar E, Pabo C.1994. Zinc finger phage: affinity selection of fingers with new DNA-binding specificities.Science,263(5147):671-673.
Reynolds L, Ullman C, Moore M, Isalan M, West M J, Clapham P, Klug A, Choo Y.2003. Repression of theHIV-15′LTR promoter and inhibition of HIV-1replication by using engineered zinc-fingertranscription factors. Proceedings of the National Academy of Sciences,100(4):1615-1620.
Ross J, Whyte J, Zhao J, Samuel M, Wells K, Prather R.2010. Optimization of square-wave electroporation fortransfection of porcine fetal fibroblasts. Transgenic Research,19(4):611-620.
Samson M, Libert F, Doranz B J, Rucker J, Liesnard C, Farber C-M, Saragosti S, Lapoumeroulie C, Cognaux J,Forceille C, Muyldermans G, Verhofstede C, Burtonboy G, Georges M, Imai T, Rana S, Yi Y, Smyth R J,Collman R G, Doms R W, Vassart G, Parmentier M.1996. Resistance to HIV-1infection in Caucasianindividuals bearing mutant alleles of the CCR-5chemokine receptor gene. Nature,382(6593):722-725.
Sander J D, Dahlborg E J, Goodwin M J, Cade L, Zhang F, Cifuentes D, Curtin S J, Blackburn J S,Thibodeau-Beganny S, Qi Y, Pierick C J, Hoffman E, Maeder M L, Khayter C, Reyon D, Dobbs D,Langenau D M, Stupar R M, Giraldez A J, Voytas D F, Peterson R T, Yeh J-R J, Joung J K.2011.Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA). Nat Meth,8(1):67-69.
Sander J D, Zaback P, Joung J K, Voytas D F, Dobbs D.2009. An affinity-based scoring scheme for predictingDNA-binding activities of modularly assembled zinc-finger proteins. Nucleic Acids Research,37(2):506-515.
Santiago Y, Chan E, Liu P-Q, Orlando S, Zhang L, Urnov F D, Holmes M C, Guschin D, Waite A, Miller J C,Rebar E J, Gregory P D, Klug A, Collingwood T N.2008. Targeted gene knockout in mammalian cells byusing engineered zinc-finger nucleases. Proceedings of the National Academy of Sciences,105(15):5809-5814.
Segal D J, Beerli R R, Blancafort P, Dreier B, Effertz K, Huber A, Koksch B, Lund C V, Magnenat L, Valente D,Barbas C F.2003. Evaluation of a Modular Strategy for the Construction of Novel Polydactyl Zinc FingerDNA-Binding Proteins. Biochemistry,42(7):2137-2148.
Segal D J, Dreier B, Beerli R R, Barbas C F.1999. Toward controlling gene expression at will: Selection anddesign of zinc finger domains recognizing each of the5′-GNN-3′DNA target sequences. Proceedingsof the National Academy of Sciences,96(6):2758-2763.
Shieh J-C2010. Bipartite Selection of Zinc Fingers by Phage Display for Any9-bp DNA Target Site#[M], TEngineered Zinc Finger Proteins:51-76.
Shukla V K, Doyon Y, Miller J C, DeKelver R C, Moehle E A, Worden S E, Mitchell J C, Arnold N L, GopalanS, Meng X, Choi V M, Rock J M, Wu Y-Y, Katibah G E, Zhifang G, McCaskill D, Simpson M A,Blakeslee B, Greenwalt S A, Butler H J, Hinkley S J, Zhang L, Rebar E J, Gregory P D, Urnov F D.2009.Precise genome modification in the crop species Zea mays using zinc-finger nucleases. Nature,459(7245):437-441.
Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck F H, Goehler H, Stroedicke M, Zenkner M, Schoenherr A,Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toks z E, Droege A,Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker E E.2005. A Human Protein-Protein InteractionNetwork: A Resource for Annotating the Proteome. Cell,122(6):957-968.
Szczepek M, Brondani V, Buchel J, Serrano L, Segal D J, Cathomen T.2007. Structure-based redesign of thedimerization interface reduces the toxicity of zinc-finger nucleases. Nat Biotech,25(7):786-793.
Takasu Y, Kobayashi I, Beumer K, Uchino K, Sezutsu H, Sajwan S, Carroll D, Tamura T, Zurovec M.2010.Targeted mutagenesis in the silkworm Bombyx mori using zinc finger nuclease mRNA injection. InsectBiochemistry and Molecular Biology,40(10):759-765.
Thomas K R, Folger K R, Capecchi M R.1986. High frequency targeting of genes to specific sites in themammalian genome. Cell,44(3):419-428.
Townsend J A, Wright D A, Winfrey R J, Fu F, Maeder M L, Joung J K, Voytas D F.2009. High-frequencymodification of plant genes using engineered zinc-finger nucleases. Nature,459(7245):442-445.
Uetz P, Giot L, Cagney G, Mansfield T A, Judson R S, Knight J R, Lockshon D, Narayan V, Srinivasan M,Pochart P, Qureshi-Emili A, Li Y, Godwin B, Conover D, Kalbfleisch T, Vijayadamodar G, Yang M,Johnston M, Fields S, Rothberg J M.2000. A comprehensive analysis of protein-protein interactions inSaccharomyces cerevisiae. Nature,403(6770):623-627.
Urnov F D, Miller J C, Lee Y-L, Beausejour C M, Rock J M, Augustus S, Jamieson A C, Porteus M H, Gregory PD, Holmes M C.2005. Highly efficient endogenous human gene correction using designed zinc-fingernucleases. Nature,435(7042):646-651.
Urnov F D, Rebar E J, Holmes M C, Zhang H S, Gregory P D.2010. Genome editing with engineered zincfinger nucleases. Nat Rev Genet,11(9):636-646.
Voytas D F.2013. Plant Genome Engineering with Sequence-Specific Nucleases. Annual Review of PlantBiology,64(1):327-350.
Watanabe M, Umeyama K, Matsunari H, Takayanagi S, Haruyama E, Nakano K, Fujiwara T, Ikezawa Y,Nakauchi H, Nagashima H.2010. Knockout of exogenous EGFP gene in porcine somatic cells usingzinc-finger nucleases. Biochemical and Biophysical Research Communications,402(1):14-18.
Wolfe S A, Greisman H A, Ramm E I, Pabo C O.1999. Analysis of zinc fingers optimized via phage display:evaluating the utility of a recognition code. Journal of Molecular Biology,285(5):1917-1934.
Wright D A, Thibodeau-Beganny S, Sander J D, Winfrey R J, Hirsh A S, Eichtinger M, Fu F, Porteus M H,Dobbs D, Voytas D F, Joung J K.2006. Standardized reagents and protocols for engineering zinc fingernucleases by modular assembly. Nat. Protocols,1(4):1637-1652.
Xiong K, Li S, Zhang H, Cui Y, Yu D, Li Y, Sun W, Fu Y, Teng Y, Liu Z, Zhou X, Xiao P, Li J, Liu H, Chen J.2013. Targeted editing of goat genome with modular-assembly zinc finger nucleases based on activityprediction by computational molecular modeling. Molecular Biology Reports,40(7):4251-4256.
Yu S, Luo J, Song Z, Ding F, Dai Y, Li N.2011. Highly efficient modification of beta-lactoglobulin (BLG) genevia zinc-finger nucleases in cattle. Cell Res,21(11):1638-1640.
Zhang F, Maeder M L, Unger-Wallace E, Hoshaw J P, Reyon D, Christian M, Li X, Pierick C J, Dobbs D,Peterson T, Joung J K, Voytas D F.2010. High frequency targeted mutagenesis in Arabidopsis thalianausing zinc finger nucleases. Proceedings of the National Academy of Sciences,107(26):12028-12033.
Zheng H, Wilson J H.1990. Gene targeting in normal and amplified cell lines. Nature,344(6262):170-173.
Zou J, Maeder M L, Mali P, Pruett-Miller S M, Thibodeau-Beganny S, Chou B-K, Chen G, Ye Z, Park I-H,Daley G Q, Porteus M H, Joung J K, Cheng L.2009. Gene Targeting of a Disease-Related Gene inHuman Induced Pluripotent Stem and Embryonic Stem Cells. Cell Stem Cell,5(1):97-110.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |