418:
modifications. ZFNickases can induce targeted HR in cultured human and livestock cells, although at lower levels than corresponding ZFNs from which they were derived because nicks can be repaired without genetic alteration. A major limitation of ZFN-mediated gene modifications is the competition between NHEJ and HR repair pathways. Regardless of the presence of a DNA donor construct, both repair mechanisms can be activated following DSBs induced by ZFNs. Thus, ZFNickases is the first plausible attempt at engineering a method to favor the HR method of DNA repair as opposed to the error-prone NHEJ repair. By reducing NHEJ repairs, ZFNickases can thereby reduce the spectrum of unwanted off-target alterations. The ease by which ZFNickases can be derive from ZFNs provides a great platform for further studies regarding the optimization of ZFNickases and possibly increasing their levels of targeted HR while still maintain their reduced NHEJ frequency.
129:
359:
consequence, yield chromosomal rearrangements and/or cell death. Off-target cleavage events may also promote random integration of donor DNA. Two separate methods have been demonstrated to decrease off-target cleavage for 3-finger ZFNs that target two adjacent 9-basepair sites. Other groups use ZFNs with 4, 5 or 6 zinc fingers that target longer and presumably rarer sites and such ZFNs could theoretically yield less off-target activity. A comparison of a pair of 3-finger ZFNs and a pair of 4-finger ZFNs detected off-target cleavage in human cells at 31 loci for the 3-finger ZFNs and at 9 loci for the 4-finger ZFNs. Whole genome sequencing of
280:
results in a heteroduplex single-strand bubble that cleavage assays can easily detect. ZFNs have also been used to modify disease-causing alleles in triplet repeat disorders. Expanded CAG/CTG repeat tracts are the genetic basis for more than a dozen inherited neurological disorders including
Huntington's disease, myotonic dystrophy, and several spinocerebellar ataxias. It has been demonstrated in human cells that ZFNs can direct double-strand breaks (DSBs) to CAG repeats and shrink the repeat from long pathological lengths to short, less toxic lengths.
300:(HR) machinery to repair the DSB using the supplied DNA fragment as a template. The HR machinery searches for homology between the damaged chromosome and the extra-chromosomal fragment and copies the sequence of the fragment between the two broken ends of the chromosome, regardless of whether the fragment contains the original sequence. If the subject is homozygous for the target allele, the efficiency of the technique is reduced since the undamaged copy of the allele may be used as a template for repair instead of the supplied fragment.
31:
288:
group of researchers in US. They suggested that the ZFN technique allows straightforward generation of a targeted allelic series of mutants; it does not rely on the existence of species-specific embryonic stem cell lines and is applicable to other vertebrates, especially those whose embryos are easily available; finally, it is also feasible to achieve targeted knock-ins in zebrafish, therefore it is possible to create human disease models that are heretofore inaccessible.
113:
utilizes a bacterial two-hybrid system and has been dubbed "OPEN" by its creators. This system combines pre-selected pools of individual zinc fingers that were each selected to bind a given triplet and then utilizes a second round of selection to obtain 3-finger arrays capable of binding a desired 9-bp sequence. This system was developed by the Zinc-Finger
Consortium as an alternative to commercial sources of engineered zinc-finger arrays.
340:
plasmids could be used to transiently express ZFNs to target a DSB to a specific gene locus in human cells, they offer an excellent way for targeted delivery of the therapeutic genes to a pre-selected chromosomal site. The ZFN-encoding plasmid-based approach has the potential to circumvent all the problems associated with the viral delivery of therapeutic genes. The first therapeutic applications of ZFNs are likely to involve
404:. TAL effector nucleases (TALENs) are particularly interesting because TAL effectors appear to be very simple to engineer and TALENs can be used to target endogenous loci in human cells. But to date no one has reported the isolation of clonal cell lines or transgenic organisms using such reagents. One type of ZFN, known as SB-728-T, has been tested for potential application in the treatment of HIV.
400:
target the desired sequence with sufficient specificity. Improved methods of engineering zinc finger domains and the availability of ZFNs from a commercial supplier now put this technology in the hands of increasing numbers of researchers. Several groups are also developing other types of engineered nucleases including engineered homing endonucleases and nucleases based on engineered
105:
zinc-finger arrays with six or more individual zinc fingers. The main drawback with this procedure is the specificities of individual zinc fingers can overlap and can depend on the context of the surrounding zinc fingers and DNA. Without methods to account for this "context dependence", the standard modular assembly procedure often fails.
153:
domains dimerize and cleave DNA, the two individual ZFNs must bind opposite strands of DNA with their C-termini a certain distance apart. The most commonly used linker sequences between the zinc finger domain and the cleavage domain requires the 5′ edge of each binding site to be separated by 5 to 7 bp.
283:
Recently, a group of researchers have successfully applied the ZFN technology to genetically modify the gol pigment gene and the ntl gene in zebrafish embryo. Specific zinc-finger motifs were engineered to recognize distinct DNA sequences. The ZFN-encoding mRNA was injected into one-cell embryos and
164:
has been employed to generate a FokI variant with enhanced cleavage activity that the authors dubbed "Sharkey". Structure-based design has also been employed to improve the cleavage specificity of FokI by modifying the dimerization interface so that only the intended heterodimeric species are active.
1684:
Goldberg AD, Banaszynski LA, Noh KM, Lewis PW, Elsaesser SJ, Stadler S, Dewell S, Law M, Guo X, Li X, Wen D, Chapgier A, Dekelver RC, Miller JC, Lee YL, Boydston EA, Holmes MC, Gregory PD, Greally JM, Rafii S, Yang C, Scambler PJ, Garrick D, Gibbons RJ, Higgs DR, Cristea IM, Urnov FD, Zheng D, Allis
1139:
Cai CQ, Doyon Y, Ainley WM, Miller JC, Dekelver RC, Moehle EA, Rock JM, Lee YL, Garrison R, Schulenberg L, Blue R, Worden A, Baker L, Faraji F, Zhang L, Holmes MC, Rebar EJ, Collingwood TN, Rubin-Wilson B, Gregory PD, Urnov FD, Petolino JF (2008). "Targeted transgene integration in plant cells using
279:
and preventing the production of the harmful protein. Multiple pairs of ZFNs can also be used to completely remove entire large segments of genomic sequence. To monitor the editing activity, a PCR of the target area amplifies both alleles and, if one contains an insertion, deletion, or mutation, it
358:
If the zinc finger domains are not specific enough for their target site or they do not target a unique site within the genome of interest, off-target cleavage may occur. Such off-target cleavage may lead to the production of enough double-strand breaks to overwhelm the repair machinery and, as a
344:
therapy using a patient's own stem cells. After editing the stem cell genome, the cells could be expanded in culture and reinserted into the patient to produce differentiated cells with corrected functions. Initial targets likely include the causes of monogenic diseases, such as the IL2Rγ gene and
417:
and thus provide for highly specific single-strand breaks in DNA. These SSBs undergo the same cellular mechanisms for DNA that ZFNs exploit, but they show a significantly reduced frequency of mutagenic NHEJ repairs at their target nicking site. This reduction provides a bias for HR-mediated gene
399:
The ability to precisely manipulate the genomes of plants and animals has numerous applications in basic research, agriculture, and human therapeutics. Using ZFNs to modify endogenous genes has traditionally been a difficult task due mainly to the challenge of generating zinc finger domains that
287:
Similar research of using ZFNs to create specific mutations in zebrafish embryo has also been carried out by other research groups. The kdr gene in zebra fish encodes for the vascular endothelial growth factor-2 receptor. Mutagenic lesions at this target site was induced using ZFN technique by a
112:
to select proteins that bound a given DNA target from a large pool of partially randomized zinc-finger arrays. More recent efforts have utilized yeast one-hybrid systems, bacterial one-hybrid and two-hybrid systems, and mammalian cells. A promising new method to select novel zinc-finger arrays
339:
I endonuclease with zinc-finger proteins (ZFPs) offer a general way to deliver a site-specific DSB to the genome, and stimulate local homologous recombination by several orders of magnitude. This makes targeted gene correction or genome editing a viable option in human cells. Since ZFN-encoding
152:
is typically used as the cleavage domain in ZFNs. This cleavage domain must dimerize in order to cleave DNA and thus a pair of ZFNs are required to target non-palindromic DNA sites. Standard ZFNs fuse the cleavage domain to the C-terminus of each zinc finger domain. To let the two cleavage
104:
repeats and can each recognize between 9 and 18 basepairs. If the zinc finger domains perfectly recognize a 3 basepair DNA sequence, they can generate a 3-finger array that can recognize a 9 basepair target site. Other procedures can utilize either 1-finger or 2-finger modules to generate
284:
a high percentage of animals carried the desired mutations and phenotypes. Their research work demonstrated that ZFNs can specifically and efficiently create heritable mutant alleles at loci of interest in the germ line, and ZFN-induced alleles can be propagated in subsequent generations.
386:
As with many foreign proteins inserted into the human body, there is a risk of an immunological response against the therapeutic agent and the cells in which it is active. Since the protein must be expressed only transiently, however, the time over which a response may develop is short.
1734:
Geurts AM, Cost GJ, Freyvert Y, Zeitler B, Miller JC, Choi VM, Jenkins SS, Wood A, Cui X, Meng X, Vincent A, Lam S, Michalkiewicz M, Schilling R, Foeckler J, Kalloway S, Weiler H, Menoret S, Anegon I, Davis GD, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Jacob HJ, Buelow R (2009).
2788:
Miller JC, Tan S, Qiao G, Barlow KA, Wang J, Xia DF, Meng X, Paschon DE, Leung E, Hinkley SJ, Dulay GP, Hua KL, Ankoudinova I, Cost GJ, Urnov FD, Zhang HS, Holmes MC, Zhang L, Gregory PD, Rebar EJ (2010). "A TALE nuclease architecture for efficient genome editing".
275:(NHEJ). NHEJ repairs DSBs by joining the two ends together and usually produces no mutations, provided that the cut is clean and uncomplicated. In some instances, however, the repair is imperfect, resulting in deletion or insertion of base-pairs, producing
132:
A pair of ZFNs, each with three zinc fingers binding to target DNA, are shown introducing a double-strand break, at the FokI domain, depicted in yellow. Subsequently, the double strand break is shown as being repaired through either
884:
Miller JC, Holmes MC, Wang J, Guschin DY, Lee YL, Rupniewski I, Beausejour CM, Waite AJ, Wang NS, Kim KA, Gregory PD, Pabo CO, Rebar EJ (2007). "An improved zinc-finger nuclease architecture for highly specific genome editing".
2058:
Tebas P, Stein D, Tang WV, Frank I, Wang S, Lee G, Spratt SK, Surosky RT, Giedlin M, Nichol G, Holmes MC, Gregory PD, Ando DG, Kalos M, Collman RG, Binder-Scholl G, Plesa G, Hwang WT, Levine B, June CH (6 March 2014).
412:
Zinc-finger nickases (ZFNickases) are created by inactivating the catalytic activity of one ZFN monomer in the ZFN dimer required for double-strand cleavage. ZFNickases demonstrate strand-specific nicking activity
2008:
Li H, Haurigot V, Doyon Y, Li T, Wong SY, Bhagwat AS, Malani N, Anguela XM, Sharma R, Ivanciu L, Murphy SL, Finn JD, Khazi FR, Zhou S, Paschon DE, Rebar EJ, Bushman FD, Gregory PD, Holmes MC, High KA (2011).
365:
modified with a pair of 5-finger ZFNs found only the intended modification and a deletion at a site "unrelated to the ZFN site" indicating this pair of ZFNs was capable of targeting a unique site in the
928:
Doyon Y, Vo TD, Mendel MC, Greenberg SG, Wang J, Xia DF, Miller JC, Urnov FD, Gregory PD, Holmes MC (2010). "Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures".
390:
Liu et al. respectively target ZFNickases to the endogenous b-casein(CSN2) locus stimulates lysostaphin and human lysozyme gene addition by homology-directed repair and derive secrete lysostaphin cows.
1541:
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".
1792:
Flisikowska T, Thorey IS, Offner S, Ros F, Lifke V, Zeitler B, Rottmann O, Vincent A, Zhang L, Jenkins S, Niersbach H, Kind AJ, Gregory PD, Schnieke AE, Platzer J (2011). Milstone DS (ed.).
2553:
Gao H, Smith J, Yang M, Jones S, Djukanovic V, Nicholson MG, West A, Bidney D, Falco SC, Jantz D, Lyznik LA (2010). "Heritable targeted mutagenesis in maize using a designed endonuclease".
1625:
Young JJ, Cherone JM, Doyon Y, Ankoudinova I, Faraji FM, Lee AH, Ngo C, Guschin DY, Paschon DE, Miller JC, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Harland RM, Zeitler B (2011).
2737:
Boch J, Scholze H, Schornack S, Hahn S, Kay S, Lahaye T, Nickstadt A, Bonas U (December 2009). "Breaking the code of DNA binding specificity of TAL-type III effectors".
1248:
Curtin SJ, Zhang F, Sander JD, Haun WJ, Starker C, Baltes NJ, Reyon D, Dahlborg EJ, Goodwin MJ, Coffman AP, Dobbs D, Joung JK, Voytas DF, Stupar RM (2011).
1394:
Wood AJ, Lo TW, Zeitler B, Pickle CS, Ralston EJ, Lee AH, Amora R, Miller JC, Leung E, Meng X, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Meyer BJ (2011).
108:
Numerous selection methods have been used to generate zinc-finger arrays capable of targeting desired sequences. Initial selection efforts utilized
68:. By taking advantage of endogenous DNA repair machinery, these reagents can be used to precisely alter the genomes of higher organisms. Alongside
1851:
Hauschild J, Petersen B, Santiago Y, Queisser AL, Carnwath JW, Lucas-Hahn A, Zhang L, Meng X, Gregory PD, Schwinzer R, Cost GJ, Niemann H (2011).
1297:
Shukla VK, Doyon Y, Miller JC, et al. (May 2009). "Precise genome modification in the crop species Zea mays using zinc-finger nucleases".
1021:
Zhang F, Maeder ML, Unger-Wallace E, Hoshaw JP, Reyon D, Christian M, Li X, Pierick CJ, Dobbs D, Peterson T, Joung JK, Voytas DF (2010).
3138:
1627:"Efficient targeted gene disruption in the soma and germ line of the frog Xenopus tropicalis using engineered zinc-finger nucleases"
267:
ZFNs can be used to disable dominant mutations in heterozygous individuals by producing double-strand breaks (DSBs) in the DNA (see
2281:
457:
17:
2299:"Zinc finger protein-dependent and -independent contributions to the in vivo off-target activity of zinc finger nucleases"
2457:"Generation of mastitis resistance in cows by targeting human lysozyme gene to -casein locus using zinc-finger nucleases"
2861:
Ramirez CL, Certo MT, Mussolino C, Goodwin MJ, Cradick TJ, McCaffrey AP, Cathomen T, Scharenberg AM, Joung JK (2012).
3197:
3187:
1348:
Bibikova M, Beumer K, Trautman J, Carroll D (2003). "Enhancing Gene
Targeting with Designed Zinc Finger Nucleases".
128:
2910:
Wang J, Friedman G, Doyon Y, Wang NS, Li CJ, Miller JC, Hua KL, Yan JE, Babiarz PD, Gregory PD, Holmes MC (2012).
160:
techniques have been employed to improve both the activity and specificity of the nuclease domain used in ZFNs.
3157:
2117:"Zinc finger nucleases: custom-designed molecular scissors for genome engineering of plant and mammalian cells"
2215:"Zinc-finger directed double-strand breaks within CAG repeat tracts promote repeat instability in human cells"
1451:
Gühmann M, Jia H, Randel N, Verasztó C, Bezares-Calderón LA, Michiels NK, Yokoyama S, Jékely G (August 2015).
256:
208:
533:"Rapid "open-source" engineering of customized zinc-finger nucleases for highly efficient gene modification"
3172:
2400:"Zinc-finger nickase-mediated insertion of the lysostaphin gene into the beta-casein locus in cloned cows"
1794:"Efficient Immunoglobulin Gene Disruption and Targeted Replacement in Rabbit Using Zinc Finger Nucleases"
335:
is simple and straightforward. Custom-designed ZFNs that combine the non-specific cleavage domain (N) of
243:, and various types of mammalian cells. Zinc finger nucleases have also been used in a mouse model of
790:"Directed Evolution of an Enhanced and Highly Efficient FokI Cleavage Domain for Zinc Finger Nucleases"
272:
138:
2833:
839:"Structure-based redesign of the dimerization interface reduces the toxicity of zinc-finger nucleases"
2912:"Targeted gene addition to a predetermined site in the human genome using a ZFN-based nicking enzyme"
2686:
Moscou MJ, Bogdanove AJ (December 2009). "A simple cipher governs DNA recognition by TAL effectors".
84:
1912:"Highly efficient modification of beta-lactoglobulin (BLG) gene via zinc-finger nucleases in cattle"
381:
297:
146:
134:
3192:
3182:
191:
2863:"Engineered zinc finger nickases induce homology-directed repair with reduced mutagenic effects"
173:
Zinc finger nucleases are useful to manipulate the genomes of many plants and animals including
3202:
2639:"TAL nucleases (TALNs): hybrid proteins composed of TAL effectors and FokI DNA-cleavage domain"
368:
361:
197:
100:
The DNA-binding domains of individual ZFNs typically contain between three and six individual
3135:
2455:
Liu X, Wang Y, Tian Y, Yu Y, Gao M, Hu G, Su F, Pan S, Luo Y, Guo Z, Quan F, Zhang Y (2014).
268:
203:
2348:"Revealing Off-Target Cleavage Specificities of Zinc Finger Nucleases by in Vitro Selection"
271:) in the mutant allele, which will, in the absence of a homologous template, be repaired by
2746:
2695:
2411:
2226:
1864:
1805:
1748:
1638:
1464:
1407:
1306:
1204:
1093:
1034:
701:
642:
174:
64:
sequences and this enables zinc-finger nucleases to target unique sequences within complex
8:
1023:"High frequency targeted mutagenesis in Arabidopsis thaliana using zinc finger nucleases"
452:
447:
442:
157:
117:
46:
2750:
2699:
2415:
2230:
1868:
1809:
1752:
1687:"Distinct Factors Control Histone Variant H3.3 Localization at Specific Genomic Regions"
1642:
1468:
1411:
1310:
1208:
1097:
1038:
705:
646:
3112:
3087:
3069:
3044:
3031:
2989:
2965:"Zinc Finger Tools: custom DNA-binding domains for transcription factors and nucleases"
2964:
2936:
2911:
2887:
2862:
2814:
2770:
2719:
2663:
2638:
2614:
2589:
2530:
2505:
2481:
2456:
2432:
2399:
2372:
2347:
2323:
2298:
2249:
2214:
2213:
Mittelman D, Moye C, Morton J, Sykoudis K, Lin Y, Carroll D, Wilson JH (16 June 2009).
2190:
2165:
2141:
2116:
2085:
2060:
2035:
2010:
1985:
1960:
1936:
1911:
1887:
1852:
1828:
1793:
1769:
1736:
1711:
1686:
1661:
1626:
1602:
1577:
1428:
1395:
1373:
1330:
1274:
1249:
1225:
1192:
1173:
1116:
1081:
1057:
1022:
998:
973:
954:
910:
866:
814:
789:
606:
581:
557:
532:
508:
483:
161:
53:
3045:"Heritable Targeted Gene Disruption in Zebrafish Using Designed Zinc Finger Nucleases"
2506:"Efficient targeting of a SCID gene by an engineered single-chain homing endonuclease"
1500:
Ochiai H, Fujita K, Suzuki KI, Nishikawa M, Shibata T, Sakamoto N, Yamamoto T (2010).
1082:"Site-directed mutagenesis in Arabidopsis using custom-designed zinc finger nucleases"
3117:
3074:
3023:
2994:
2941:
2892:
2806:
2774:
2762:
2711:
2668:
2619:
2570:
2566:
2535:
2486:
2437:
2377:
2328:
2277:
2254:
2195:
2146:
2090:
2040:
1990:
1941:
1892:
1833:
1774:
1716:
1666:
1607:
1558:
1523:
1518:
1482:
1433:
1365:
1322:
1279:
1230:
1165:
1157:
1121:
1062:
1003:
946:
914:
902:
858:
819:
770:
729:
724:
689:
670:
665:
630:
611:
562:
513:
427:
345:
the β-globin gene for gene correction and CCR5 gene for mutagenesis and disablement.
3035:
2818:
1453:"Spectral Tuning of Phototaxis by a Go-Opsin in the Rhabdomeric Eyes of Platynereis"
1377:
958:
870:
3107:
3099:
3064:
3056:
3015:
3006:
Porteus MH, Carroll D (August 2005). "Gene targeting using zinc finger nucleases".
2984:
2976:
2931:
2923:
2882:
2874:
2798:
2754:
2723:
2703:
2658:
2650:
2609:
2601:
2562:
2525:
2517:
2476:
2468:
2427:
2419:
2367:
2359:
2318:
2310:
2244:
2234:
2185:
2177:
2136:
2128:
2080:
2072:
2030:
2022:
1980:
1972:
1931:
1923:
1882:
1872:
1823:
1813:
1764:
1756:
1706:
1698:
1656:
1646:
1597:
1589:
1550:
1513:
1472:
1423:
1415:
1357:
1334:
1314:
1269:
1261:
1220:
1212:
1193:"High-frequency modification of plant genes using engineered zinc-finger nucleases"
1177:
1149:
1111:
1101:
1052:
1042:
993:
985:
938:
894:
850:
809:
801:
760:
719:
709:
660:
650:
601:
593:
552:
544:
503:
495:
1853:"Efficient generation of a biallelic knockout in pigs using zinc-finger nucleases"
3142:
1818:
1191:
Townsend JA, Wright DA, Winfrey RJ, Fu F, Maeder ML, Joung JK, Voytas DF (2009).
548:
325:
255:. ZFNs are also used to create a new generation of genetic disease models called
3088:"Targeted gene inactivation in zebrafish using engineered zinc finger nucleases"
2605:
1250:"Targeted Mutagenesis of Duplicated Genes in Soybean with Zinc-Finger Nucleases"
597:
251:
gene disrupted by zinc finger nucleases to be safe as a potential treatment for
30:
3177:
2219:
Proceedings of the
National Academy of Sciences of the United States of America
1702:
1554:
838:
437:
432:
77:
1477:
1452:
1153:
989:
805:
308:
The success of gene therapy depends on the efficient insertion of therapeutic
3166:
2061:"Gene Editing of CCR5 in Autologous CD4 T Cells of Persons Infected with HIV"
2011:"In vivo genome editing restores haemostasis in a mouse model of haemophilia"
1161:
714:
109:
2758:
2707:
2239:
1877:
1760:
1651:
1419:
1361:
1106:
1047:
971:
3121:
3078:
3027:
2998:
2945:
2896:
2810:
2766:
2715:
2672:
2623:
2574:
2539:
2490:
2472:
2441:
2381:
2332:
2258:
2199:
2166:"Targeted chromosomal deletions in human cells using zinc finger nucleases"
2150:
2094:
2044:
1994:
1945:
1896:
1837:
1778:
1720:
1670:
1611:
1562:
1527:
1502:"Targeted mutagenesis in the sea urchin embryo using zinc-finger nucleases"
1501:
1486:
1437:
1369:
1326:
1283:
1234:
1169:
1125:
1066:
1007:
950:
906:
862:
823:
774:
655:
615:
566:
517:
401:
2927:
2398:
Liu X, Wang YS, Guo WJ, Chang BH, Liu J, Guo ZK, Quan FS, Zhang Y (2013).
2181:
2115:
Durai S, Mani M, Kandavelou K, Wu J, Porteus MH, Chandrasegaran S (2005).
2076:
1593:
1265:
837:
Szczepek M, Brondani V, Büchel J, Serrano L, Segal DJ, Cathomen T (2007).
733:
674:
631:"Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain"
499:
484:"Unexpected failure rates for modular assembly of engineered zinc fingers"
2980:
2878:
2654:
2521:
2314:
2132:
332:
321:
276:
244:
101:
50:
2026:
1976:
1927:
1318:
1216:
765:
748:
296:
ZFNs are also used to rewrite the sequence of an allele by invoking the
2423:
2363:
942:
313:
2802:
216:
3103:
3060:
3019:
2272:
Kandavelou K, Chandrasegaran S (2008). "Plasmids for Gene
Therapy".
898:
854:
60:. Zinc finger domains can be engineered to target specific desired
974:"Creating Designed Zinc-Finger Nucleases with Minimal Cytotoxicity"
972:
Ramalingam S, Kandavelou K, Rajenderan R, Chandrasegaran S (2011).
252:
212:
57:
1737:"Knockout Rats via Embryo Microinjection of Zinc-Finger Nucleases"
1850:
462:
329:
182:
178:
2590:"Targeting DNA Double-Strand Breaks with TAL Effector Nucleases"
2297:
Gupta A, Meng X, Zhu LJ, Lawson ND, Wolfe SA (September 2010).
317:
240:
232:
69:
65:
1396:"Targeted Genome Editing Across Species Using ZFNs and TALENs"
1020:
3152:
3147:
2504:
Grizot S, Smith J, Daboussi F, et al. (September 2009).
1347:
836:
186:
73:
2860:
1624:
3086:
Meng X, Noyes MB, Zhu LJ, Lawson ND, Wolfe SA (June 2008).
2212:
1683:
1540:
1499:
309:
248:
224:
220:
149:
3043:
Doyon Y, McCammon JM, Miller JC, et al. (June 2008).
2588:
Christian M, Cermak T, Doyle EL, et al. (July 2010).
1791:
2345:
1733:
688:
Bitinaite J, Wah, DA, Aggarwal AK, Schildkraut I (1998).
482:
Ramirez CL, Foley JE, Wright DA, et al. (May 2008).
236:
228:
61:
2736:
2271:
1578:"Zinc Finger–Based Knockout Punches for Zebrafish Genes"
1450:
2461:
Proceedings of the Royal
Society B: Biological Sciences
1190:
883:
247:
and a clinical trial found CD4+ human T-cells with the
927:
687:
2909:
2114:
1247:
2834:"Zinc Fingers Could Be Key to Reviving Gene Therapy"
2637:
Li T, Huang S, Jiang WZ, et al. (August 2010).
2587:
1138:
749:"Zinc-finger nucleases: the next generation emerges"
628:
3042:
2787:
2503:
2346:Pattanayak V, Ramirez CL, Joung JK, Liu DR (2011).
2057:
1393:
145:The non-specific cleavage domain from the type IIs
120:for more info on zinc finger selection techniques)
3085:
2296:
1079:
481:
2552:
2007:
1910:Yu S, Luo J, Song Z, Ding F, Dai Y, Li N (2011).
1296:
3164:
690:"FokI dimerization is required for DNA cleavage"
573:
2685:
2397:
1857:Proceedings of the National Academy of Sciences
1785:
1631:Proceedings of the National Academy of Sciences
1086:Proceedings of the National Academy of Sciences
1027:Proceedings of the National Academy of Sciences
582:"Genome engineering with zinc-finger nucleases"
3005:
2339:
1961:"Zinc-finger Nucleases as Gene Therapy Agents"
965:
3153:Zinc Finger Consortium materials from Addgene
2962:
2454:
1909:
1844:
746:
2636:
2274:Plasmids: Current Research and Future Trends
1677:
1444:
1341:
1184:
787:
681:
2856:
2854:
1534:
1389:
1387:
1073:
830:
2781:
2265:
1727:
1241:
76:, ZFN is a prominent tool in the field of
3111:
3068:
2988:
2935:
2886:
2662:
2613:
2529:
2480:
2431:
2371:
2322:
2248:
2238:
2189:
2163:
2140:
2084:
2051:
2034:
1984:
1935:
1886:
1876:
1827:
1817:
1768:
1710:
1660:
1650:
1618:
1601:
1543:Insect Biochemistry and Molecular Biology
1517:
1476:
1427:
1273:
1224:
1115:
1105:
1056:
1046:
1014:
997:
921:
877:
813:
764:
723:
713:
664:
654:
605:
556:
531:Maeder ML, et al. (September 2008).
507:
2851:
2825:
2110:
2108:
2106:
2104:
1384:
629:Kim YG, Cha J, Chandrasegaran S (1996).
127:
29:
2164:Lee HJ, Kim E, Kim JS (December 2009).
1958:
1132:
579:
407:
83:It was initially created by researcher
14:
3165:
2393:
2391:
2001:
1903:
781:
622:
530:
353:
262:
123:
2448:
2101:
1575:
1080:Osakabe K, Osakabe Y, Toki S (2010).
458:Zinc finger nuclease treatment of HIV
348:
95:
2903:
2831:
2963:Mandell JG, Barbas CF (July 2006).
2388:
2276:. Norfolk: Caister Academic Press.
24:
2956:
747:Cathomen T, Joung JK (July 2008).
25:
3214:
3129:
1140:designed zinc finger nucleases".
375:
291:
2567:10.1111/j.1365-313X.2009.04041.x
1519:10.1111/j.1365-2443.2010.01425.x
788:Guo J, Gaj T, Barbas CF (2010).
2730:
2679:
2630:
2581:
2546:
2497:
2290:
2206:
2157:
2065:New England Journal of Medicine
1952:
1569:
1493:
1290:
320:, without causing cell injury,
303:
168:
3148:Zinc Finger Consortium website
740:
524:
475:
13:
1:
3158:A commercial supplier of ZFNs
2975:(Web Server issue): W516–23.
468:
316:target site within the human
257:isogenic human disease models
34:The schematic diagram of ZFNs
1819:10.1371/journal.pone.0021045
978:Journal of Molecular Biology
794:Journal of Molecular Biology
549:10.1016/j.molcel.2008.06.016
394:
7:
2832:Wade N (28 December 2009).
2606:10.1534/genetics.110.120717
598:10.1534/genetics.111.131433
421:
10:
3219:
1703:10.1016/j.cell.2010.01.003
1555:10.1016/j.ibmb.2010.07.012
379:
273:non-homologous end-joining
139:non-homologous end joining
90:
3141:17 September 2009 at the
1478:10.1016/j.cub.2015.07.017
1154:10.1007/s11103-008-9449-7
990:10.1016/j.jmb.2010.10.043
806:10.1016/j.jmb.2010.04.060
85:Srinivasan Chandrasegaran
3198:Repetitive DNA sequences
3188:History of biotechnology
715:10.1073/pnas.95.18.10570
382:Adaptive immune response
298:homologous recombination
147:restriction endonuclease
135:homology-directed repair
2759:10.1126/science.1178811
2708:10.1126/science.1178817
2240:10.1073/pnas.0902420106
1878:10.1073/pnas.1106422108
1761:10.1126/science.1172447
1652:10.1073/pnas.1102030108
1420:10.1126/science.1207773
1362:10.1126/science.1079512
1142:Plant Molecular Biology
1107:10.1073/pnas.1000234107
1048:10.1073/pnas.0914991107
192:Drosophila melanogaster
2867:Nucleic Acids Research
2473:10.1098/rspb.2013.3368
694:Proc Natl Acad Sci USA
656:10.1073/pnas.93.3.1156
635:Proc Natl Acad Sci USA
328:. The construction of
142:
49:generated by fusing a
35:
2928:10.1101/gr.122879.111
2404:Nature Communications
2182:10.1101/gr.099747.109
2077:10.1056/NEJMoa1300662
1594:10.1089/zeb.2008.9988
1266:10.1104/pp.111.172981
500:10.1038/nmeth0508-374
380:Further information:
269:Genetic recombination
204:Platynereis dumerilii
131:
39:Zinc-finger nucleases
33:
3136:Zinc finger selector
2791:Nature Biotechnology
887:Nature Biotechnology
843:Nature Biotechnology
408:Zinc-finger nickases
18:Zinc finger nuclease
3173:Engineered proteins
2751:2009Sci...326.1509B
2745:(5959): 1509–1512.
2700:2009Sci...326.1501M
2416:2013NatCo...4.2565L
2231:2009PNAS..106.9607M
2027:10.1038/nature10177
1977:10.1038/gt.2008.145
1928:10.1038/cr.2011.153
1869:2011PNAS..10812013H
1863:(29): 12013–12017.
1810:2011PLoSO...621045F
1753:2009Sci...325..433G
1643:2011PNAS..108.7052Y
1469:2015CBio...25.2265G
1412:2011Sci...333..307W
1319:10.1038/nature07992
1311:2009Natur.459..437S
1217:10.1038/nature07845
1209:2009Natur.459..442T
1098:2010PNAS..10712034O
1092:(26): 12034–12039.
1039:2010PNAS..10712028Z
1033:(26): 12028–12033.
766:10.1038/mt.2008.114
706:1998PNAS...9510570B
700:(18): 10570–10575.
647:1996PNAS...93.1156K
453:Protein engineering
448:Zinc finger chimera
443:Zinc finger protein
354:Off-target cleavage
263:Disabling an allele
158:protein engineering
124:DNA-cleavage domain
118:Zinc finger chimera
58:DNA-cleavage domain
47:restriction enzymes
2981:10.1093/nar/gkl209
2879:10.1093/nar/gks179
2838:The New York Times
2655:10.1093/nar/gkq704
2522:10.1093/nar/gkp548
2467:(1780): 20133368.
2424:10.1038/ncomms3565
2364:10.1038/nmeth.1670
2315:10.1093/nar/gkq787
2133:10.1093/nar/gki912
1959:Carroll D (2008).
943:10.1038/nmeth.1539
580:Carroll D (2011).
349:Potential problems
312:at an appropriate
162:Directed evolution
156:Several different
143:
96:DNA-binding domain
54:DNA-binding domain
36:
27:Artificial enzymes
2969:Nucleic Acids Res
2643:Nucleic Acids Res
2555:The Plant Journal
2516:(16): 5405–5419.
2510:Nucleic Acids Res
2303:Nucleic Acids Res
2283:978-1-904455-35-6
2225:(24): 9607–9612.
2127:(18): 5978–5990.
2121:Nucleic Acids Res
2021:(7355): 217–221.
1971:(22): 1463–1468.
1922:(11): 1638–1640.
1637:(17): 7052–7057.
1576:Ekker SC (2008).
1463:(17): 2265–2271.
1305:(7245): 437–441.
1203:(7245): 442–445.
428:Chimeric nuclease
324:mutations, or an
45:) are artificial
16:(Redirected from
3210:
3125:
3115:
3082:
3072:
3039:
3002:
2992:
2950:
2949:
2939:
2922:(4): 1316–1326.
2907:
2901:
2900:
2890:
2873:(7): 5560–5568.
2858:
2849:
2848:
2846:
2844:
2829:
2823:
2822:
2803:10.1038/nbt.1755
2785:
2779:
2778:
2734:
2728:
2727:
2683:
2677:
2676:
2666:
2634:
2628:
2627:
2617:
2585:
2579:
2578:
2550:
2544:
2543:
2533:
2501:
2495:
2494:
2484:
2452:
2446:
2445:
2435:
2395:
2386:
2385:
2375:
2343:
2337:
2336:
2326:
2294:
2288:
2287:
2269:
2263:
2262:
2252:
2242:
2210:
2204:
2203:
2193:
2161:
2155:
2154:
2144:
2112:
2099:
2098:
2088:
2055:
2049:
2048:
2038:
2005:
1999:
1998:
1988:
1956:
1950:
1949:
1939:
1907:
1901:
1900:
1890:
1880:
1848:
1842:
1841:
1831:
1821:
1789:
1783:
1782:
1772:
1731:
1725:
1724:
1714:
1681:
1675:
1674:
1664:
1654:
1622:
1616:
1615:
1605:
1588:(2): 1121–1123.
1573:
1567:
1566:
1538:
1532:
1531:
1521:
1497:
1491:
1490:
1480:
1448:
1442:
1441:
1431:
1391:
1382:
1381:
1345:
1339:
1338:
1294:
1288:
1287:
1277:
1254:Plant Physiology
1245:
1239:
1238:
1228:
1188:
1182:
1181:
1136:
1130:
1129:
1119:
1109:
1077:
1071:
1070:
1060:
1050:
1018:
1012:
1011:
1001:
969:
963:
962:
925:
919:
918:
881:
875:
874:
834:
828:
827:
817:
785:
779:
778:
768:
759:(7): 1200–1207.
744:
738:
737:
727:
717:
685:
679:
678:
668:
658:
641:(3): 1156–1160.
626:
620:
619:
609:
577:
571:
570:
560:
528:
522:
521:
511:
479:
21:
3218:
3217:
3213:
3212:
3211:
3209:
3208:
3207:
3163:
3162:
3143:Wayback Machine
3132:
3104:10.1038/nbt1398
3092:Nat. Biotechnol
3061:10.1038/nbt1409
3049:Nat. Biotechnol
3020:10.1038/nbt1125
3008:Nat. Biotechnol
2959:
2957:Further reading
2954:
2953:
2916:Genome Research
2908:
2904:
2859:
2852:
2842:
2840:
2830:
2826:
2786:
2782:
2735:
2731:
2684:
2680:
2635:
2631:
2586:
2582:
2551:
2547:
2502:
2498:
2453:
2449:
2396:
2389:
2344:
2340:
2295:
2291:
2284:
2270:
2266:
2211:
2207:
2162:
2158:
2113:
2102:
2071:(10): 901–910.
2056:
2052:
2006:
2002:
1957:
1953:
1908:
1904:
1849:
1845:
1790:
1786:
1732:
1728:
1682:
1678:
1623:
1619:
1574:
1570:
1549:(10): 759–765.
1539:
1535:
1498:
1494:
1457:Current Biology
1449:
1445:
1392:
1385:
1346:
1342:
1295:
1291:
1246:
1242:
1189:
1185:
1137:
1133:
1078:
1074:
1019:
1015:
970:
966:
926:
922:
899:10.1038/nbt1319
882:
878:
855:10.1038/nbt1317
835:
831:
786:
782:
745:
741:
686:
682:
627:
623:
578:
574:
529:
525:
480:
476:
471:
424:
410:
397:
384:
378:
356:
351:
326:immune response
306:
294:
265:
171:
126:
98:
93:
28:
23:
22:
15:
12:
11:
5:
3216:
3206:
3205:
3200:
3195:
3193:Non-coding RNA
3190:
3185:
3183:Genome editing
3180:
3175:
3161:
3160:
3155:
3150:
3145:
3131:
3130:External links
3128:
3127:
3126:
3098:(6): 695–701.
3083:
3055:(6): 702–708.
3040:
3014:(8): 967–973.
3003:
2958:
2955:
2952:
2951:
2902:
2850:
2824:
2797:(2): 143–148.
2780:
2729:
2694:(5959): 1501.
2678:
2649:(1): 359–372.
2629:
2600:(2): 757–761.
2580:
2561:(1): 176–187.
2545:
2496:
2447:
2387:
2358:(9): 765–770.
2352:Nature Methods
2338:
2309:(1): 381–392.
2289:
2282:
2264:
2205:
2156:
2100:
2050:
2000:
1951:
1902:
1843:
1784:
1726:
1697:(5): 678–691.
1676:
1617:
1568:
1533:
1512:(8): 875–885.
1506:Genes to Cells
1492:
1443:
1383:
1340:
1289:
1260:(2): 466–473.
1240:
1183:
1148:(6): 699–709.
1131:
1072:
1013:
984:(3): 630–641.
964:
931:Nature Methods
920:
893:(7): 778–785.
876:
849:(7): 786–793.
829:
780:
739:
680:
621:
592:(4): 773–782.
572:
543:(2): 294–301.
523:
494:(5): 374–375.
473:
472:
470:
467:
466:
465:
460:
455:
450:
445:
440:
438:Gene targeting
435:
433:Genome editing
430:
423:
420:
409:
406:
396:
393:
377:
376:Immunogenicity
374:
355:
352:
350:
347:
305:
302:
293:
292:Allele editing
290:
264:
261:
170:
167:
125:
122:
97:
94:
92:
89:
78:genome editing
26:
9:
6:
4:
3:
2:
3215:
3204:
3203:Zinc proteins
3201:
3199:
3196:
3194:
3191:
3189:
3186:
3184:
3181:
3179:
3176:
3174:
3171:
3170:
3168:
3159:
3156:
3154:
3151:
3149:
3146:
3144:
3140:
3137:
3134:
3133:
3123:
3119:
3114:
3109:
3105:
3101:
3097:
3093:
3089:
3084:
3080:
3076:
3071:
3066:
3062:
3058:
3054:
3050:
3046:
3041:
3037:
3033:
3029:
3025:
3021:
3017:
3013:
3009:
3004:
3000:
2996:
2991:
2986:
2982:
2978:
2974:
2970:
2966:
2961:
2960:
2947:
2943:
2938:
2933:
2929:
2925:
2921:
2917:
2913:
2906:
2898:
2894:
2889:
2884:
2880:
2876:
2872:
2868:
2864:
2857:
2855:
2839:
2835:
2828:
2820:
2816:
2812:
2808:
2804:
2800:
2796:
2792:
2784:
2776:
2772:
2768:
2764:
2760:
2756:
2752:
2748:
2744:
2740:
2733:
2725:
2721:
2717:
2713:
2709:
2705:
2701:
2697:
2693:
2689:
2682:
2674:
2670:
2665:
2660:
2656:
2652:
2648:
2644:
2640:
2633:
2625:
2621:
2616:
2611:
2607:
2603:
2599:
2595:
2591:
2584:
2576:
2572:
2568:
2564:
2560:
2556:
2549:
2541:
2537:
2532:
2527:
2523:
2519:
2515:
2511:
2507:
2500:
2492:
2488:
2483:
2478:
2474:
2470:
2466:
2462:
2458:
2451:
2443:
2439:
2434:
2429:
2425:
2421:
2417:
2413:
2409:
2405:
2401:
2394:
2392:
2383:
2379:
2374:
2369:
2365:
2361:
2357:
2353:
2349:
2342:
2334:
2330:
2325:
2320:
2316:
2312:
2308:
2304:
2300:
2293:
2285:
2279:
2275:
2268:
2260:
2256:
2251:
2246:
2241:
2236:
2232:
2228:
2224:
2220:
2216:
2209:
2201:
2197:
2192:
2187:
2183:
2179:
2175:
2171:
2167:
2160:
2152:
2148:
2143:
2138:
2134:
2130:
2126:
2122:
2118:
2111:
2109:
2107:
2105:
2096:
2092:
2087:
2082:
2078:
2074:
2070:
2066:
2062:
2054:
2046:
2042:
2037:
2032:
2028:
2024:
2020:
2016:
2012:
2004:
1996:
1992:
1987:
1982:
1978:
1974:
1970:
1966:
1962:
1955:
1947:
1943:
1938:
1933:
1929:
1925:
1921:
1917:
1916:Cell Research
1913:
1906:
1898:
1894:
1889:
1884:
1879:
1874:
1870:
1866:
1862:
1858:
1854:
1847:
1839:
1835:
1830:
1825:
1820:
1815:
1811:
1807:
1804:(6): e21045.
1803:
1799:
1795:
1788:
1780:
1776:
1771:
1766:
1762:
1758:
1754:
1750:
1747:(5939): 433.
1746:
1742:
1738:
1730:
1722:
1718:
1713:
1708:
1704:
1700:
1696:
1692:
1688:
1680:
1672:
1668:
1663:
1658:
1653:
1648:
1644:
1640:
1636:
1632:
1628:
1621:
1613:
1609:
1604:
1599:
1595:
1591:
1587:
1583:
1579:
1572:
1564:
1560:
1556:
1552:
1548:
1544:
1537:
1529:
1525:
1520:
1515:
1511:
1507:
1503:
1496:
1488:
1484:
1479:
1474:
1470:
1466:
1462:
1458:
1454:
1447:
1439:
1435:
1430:
1425:
1421:
1417:
1413:
1409:
1406:(6040): 307.
1405:
1401:
1397:
1390:
1388:
1379:
1375:
1371:
1367:
1363:
1359:
1356:(5620): 764.
1355:
1351:
1344:
1336:
1332:
1328:
1324:
1320:
1316:
1312:
1308:
1304:
1300:
1293:
1285:
1281:
1276:
1271:
1267:
1263:
1259:
1255:
1251:
1244:
1236:
1232:
1227:
1222:
1218:
1214:
1210:
1206:
1202:
1198:
1194:
1187:
1179:
1175:
1171:
1167:
1163:
1159:
1155:
1151:
1147:
1143:
1135:
1127:
1123:
1118:
1113:
1108:
1103:
1099:
1095:
1091:
1087:
1083:
1076:
1068:
1064:
1059:
1054:
1049:
1044:
1040:
1036:
1032:
1028:
1024:
1017:
1009:
1005:
1000:
995:
991:
987:
983:
979:
975:
968:
960:
956:
952:
948:
944:
940:
936:
932:
924:
916:
912:
908:
904:
900:
896:
892:
888:
880:
872:
868:
864:
860:
856:
852:
848:
844:
840:
833:
825:
821:
816:
811:
807:
803:
800:(1): 96–107.
799:
795:
791:
784:
776:
772:
767:
762:
758:
754:
750:
743:
735:
731:
726:
721:
716:
711:
707:
703:
699:
695:
691:
684:
676:
672:
667:
662:
657:
652:
648:
644:
640:
636:
632:
625:
617:
613:
608:
603:
599:
595:
591:
587:
583:
576:
568:
564:
559:
554:
550:
546:
542:
538:
534:
527:
519:
515:
510:
505:
501:
497:
493:
489:
485:
478:
474:
464:
461:
459:
456:
454:
451:
449:
446:
444:
441:
439:
436:
434:
431:
429:
426:
425:
419:
416:
405:
403:
402:TAL effectors
392:
388:
383:
373:
371:
370:
364:
363:
346:
343:
338:
334:
331:
327:
323:
319:
315:
311:
301:
299:
289:
285:
281:
278:
274:
270:
260:
258:
254:
250:
246:
242:
238:
234:
230:
226:
222:
218:
214:
210:
206:
205:
200:
199:
194:
193:
188:
184:
180:
176:
166:
163:
159:
154:
151:
148:
140:
136:
130:
121:
119:
114:
111:
110:phage display
106:
103:
88:
86:
81:
79:
75:
71:
67:
63:
59:
55:
52:
48:
44:
40:
32:
19:
3095:
3091:
3052:
3048:
3011:
3007:
2972:
2968:
2919:
2915:
2905:
2870:
2866:
2841:. Retrieved
2837:
2827:
2794:
2790:
2783:
2742:
2738:
2732:
2691:
2687:
2681:
2646:
2642:
2632:
2597:
2593:
2583:
2558:
2554:
2548:
2513:
2509:
2499:
2464:
2460:
2450:
2407:
2403:
2355:
2351:
2341:
2306:
2302:
2292:
2273:
2267:
2222:
2218:
2208:
2176:(1): 81–89.
2173:
2169:
2159:
2124:
2120:
2068:
2064:
2053:
2018:
2014:
2003:
1968:
1965:Gene Therapy
1964:
1954:
1919:
1915:
1905:
1860:
1856:
1846:
1801:
1797:
1787:
1744:
1740:
1729:
1694:
1690:
1679:
1634:
1630:
1620:
1585:
1581:
1571:
1546:
1542:
1536:
1509:
1505:
1495:
1460:
1456:
1446:
1403:
1399:
1353:
1349:
1343:
1302:
1298:
1292:
1257:
1253:
1243:
1200:
1196:
1186:
1145:
1141:
1134:
1089:
1085:
1075:
1030:
1026:
1016:
981:
977:
967:
937:(1): 74–79.
934:
930:
923:
890:
886:
879:
846:
842:
832:
797:
793:
783:
756:
752:
742:
697:
693:
683:
638:
634:
624:
589:
585:
575:
540:
536:
526:
491:
488:Nat. Methods
487:
477:
414:
411:
398:
389:
385:
367:
360:
357:
341:
336:
307:
304:Gene therapy
295:
286:
282:
266:
202:
196:
190:
172:
169:Applications
155:
144:
115:
107:
99:
82:
42:
38:
37:
1685:CD (2010).
314:chromosomal
277:frame-shift
245:haemophilia
175:arabidopsis
102:zinc finger
70:CRISPR/Cas9
51:zinc finger
3167:Categories
2170:Genome Res
469:References
369:C. elegans
362:C. elegans
209:sea urchin
198:C. elegans
2775:206522347
1582:Zebrafish
1162:0167-4412
915:205273515
753:Mol. Ther
537:Mol. Cell
395:Prospects
322:oncogenic
217:zebrafish
3139:Archived
3122:18500337
3079:18500334
3036:13221399
3028:16082368
2999:16845061
2946:22434427
2897:22373919
2819:53549397
2811:21179091
2767:19933107
2716:19933106
2673:20699274
2624:20660643
2594:Genetics
2575:19811621
2540:19584299
2491:24552841
2442:24121612
2410:: 2565.
2382:21822273
2333:20843781
2259:19482946
2200:19952142
2151:16251401
2095:24597865
2045:21706032
1995:18784746
1946:21912434
1897:21730124
1838:21695153
1798:PLOS ONE
1779:19628861
1721:20211137
1671:21471457
1612:18554175
1563:20692340
1528:20604805
1487:26255845
1438:21700836
1378:42087531
1370:12730594
1327:19404259
1284:21464476
1235:19404258
1170:19112554
1126:20508151
1067:20508152
1008:21094162
959:14334237
951:21131970
907:17603475
871:22079561
863:17603476
824:20447404
775:18545224
616:21828278
586:Genetics
567:18657511
518:18446154
422:See also
415:in vitro
372:genome.
253:HIV/AIDS
213:silkworm
3113:2502069
3070:2674762
2990:1538883
2937:3396372
2888:3384306
2747:Bibcode
2739:Science
2724:6648530
2696:Bibcode
2688:Science
2664:3017587
2615:2942870
2531:2760784
2482:4027401
2433:3826644
2412:Bibcode
2373:3164905
2324:3017618
2250:2701052
2227:Bibcode
2191:2798833
2142:1270952
2086:4084652
2036:3152293
1986:2747807
1937:3364726
1888:3141985
1865:Bibcode
1829:3113902
1806:Bibcode
1770:2831805
1749:Bibcode
1741:Science
1712:2885838
1662:3084115
1639:Bibcode
1603:2849655
1465:Bibcode
1429:3489282
1408:Bibcode
1400:Science
1350:Science
1335:4323298
1307:Bibcode
1275:3177250
1226:2743854
1205:Bibcode
1178:6826269
1117:2900650
1094:Bibcode
1058:2900673
1035:Bibcode
999:3017627
815:2885538
734:9724744
702:Bibcode
675:8577732
643:Bibcode
607:3176093
558:2535758
509:7880305
463:CompoZr
342:ex vivo
333:vectors
330:plasmid
233:rabbits
183:soybean
179:tobacco
91:Domains
66:genomes
3120:
3110:
3077:
3067:
3034:
3026:
2997:
2987:
2944:
2934:
2895:
2885:
2843:31 May
2817:
2809:
2773:
2765:
2722:
2714:
2671:
2661:
2622:
2612:
2573:
2538:
2528:
2489:
2479:
2440:
2430:
2380:
2370:
2331:
2321:
2280:
2257:
2247:
2198:
2188:
2149:
2139:
2093:
2083:
2043:
2033:
2015:Nature
1993:
1983:
1944:
1934:
1895:
1885:
1836:
1826:
1777:
1767:
1719:
1709:
1669:
1659:
1610:
1600:
1561:
1526:
1485:
1436:
1426:
1376:
1368:
1333:
1325:
1299:Nature
1282:
1272:
1233:
1223:
1197:Nature
1176:
1168:
1160:
1124:
1114:
1065:
1055:
1006:
996:
957:
949:
913:
905:
869:
861:
822:
812:
773:
732:
722:
673:
663:
614:
604:
565:
555:
516:
506:
318:genome
241:cattle
116:(see:
3178:Genes
3032:S2CID
2815:S2CID
2771:S2CID
2720:S2CID
1374:S2CID
1331:S2CID
1174:S2CID
955:S2CID
911:S2CID
867:S2CID
725:27935
666:40048
310:genes
221:frogs
74:TALEN
56:to a
3118:PMID
3075:PMID
3024:PMID
2995:PMID
2942:PMID
2893:PMID
2845:2016
2807:PMID
2763:PMID
2712:PMID
2669:PMID
2620:PMID
2571:PMID
2536:PMID
2487:PMID
2438:PMID
2378:PMID
2329:PMID
2278:ISBN
2255:PMID
2196:PMID
2147:PMID
2091:PMID
2041:PMID
1991:PMID
1942:PMID
1893:PMID
1834:PMID
1775:PMID
1717:PMID
1691:Cell
1667:PMID
1608:PMID
1559:PMID
1524:PMID
1483:PMID
1434:PMID
1366:PMID
1323:PMID
1280:PMID
1231:PMID
1166:PMID
1158:ISSN
1122:PMID
1063:PMID
1004:PMID
947:PMID
903:PMID
859:PMID
820:PMID
771:PMID
730:PMID
671:PMID
612:PMID
563:PMID
514:PMID
249:CCR5
237:pigs
229:rats
225:mice
211:,
187:corn
150:FokI
72:and
43:ZFNs
3108:PMC
3100:doi
3065:PMC
3057:doi
3016:doi
2985:PMC
2977:doi
2932:PMC
2924:doi
2883:PMC
2875:doi
2799:doi
2755:doi
2743:326
2704:doi
2692:326
2659:PMC
2651:doi
2610:PMC
2602:doi
2598:186
2563:doi
2526:PMC
2518:doi
2477:PMC
2469:doi
2465:281
2428:PMC
2420:doi
2368:PMC
2360:doi
2319:PMC
2311:doi
2245:PMC
2235:doi
2223:106
2186:PMC
2178:doi
2137:PMC
2129:doi
2081:PMC
2073:doi
2069:370
2031:PMC
2023:doi
2019:475
1981:PMC
1973:doi
1932:PMC
1924:doi
1883:PMC
1873:doi
1861:108
1824:PMC
1814:doi
1765:PMC
1757:doi
1745:325
1707:PMC
1699:doi
1695:140
1657:PMC
1647:doi
1635:108
1598:PMC
1590:doi
1551:doi
1514:doi
1473:doi
1424:PMC
1416:doi
1404:333
1358:doi
1354:300
1315:doi
1303:459
1270:PMC
1262:doi
1258:156
1221:PMC
1213:doi
1201:459
1150:doi
1112:PMC
1102:doi
1090:107
1053:PMC
1043:doi
1031:107
994:PMC
986:doi
982:405
939:doi
895:doi
851:doi
810:PMC
802:doi
798:400
761:doi
720:PMC
710:doi
661:PMC
651:doi
602:PMC
594:doi
590:188
553:PMC
545:doi
504:PMC
496:doi
337:Fok
215:,
137:or
62:DNA
3169::
3116:.
3106:.
3096:26
3094:.
3090:.
3073:.
3063:.
3053:26
3051:.
3047:.
3030:.
3022:.
3012:23
3010:.
2993:.
2983:.
2973:34
2971:.
2967:.
2940:.
2930:.
2920:22
2918:.
2914:.
2891:.
2881:.
2871:40
2869:.
2865:.
2853:^
2836:.
2813:.
2805:.
2795:29
2793:.
2769:.
2761:.
2753:.
2741:.
2718:.
2710:.
2702:.
2690:.
2667:.
2657:.
2647:39
2645:.
2641:.
2618:.
2608:.
2596:.
2592:.
2569:.
2559:61
2557:.
2534:.
2524:.
2514:37
2512:.
2508:.
2485:.
2475:.
2463:.
2459:.
2436:.
2426:.
2418:.
2406:.
2402:.
2390:^
2376:.
2366:.
2354:.
2350:.
2327:.
2317:.
2307:39
2305:.
2301:.
2253:.
2243:.
2233:.
2221:.
2217:.
2194:.
2184:.
2174:20
2172:.
2168:.
2145:.
2135:.
2125:33
2123:.
2119:.
2103:^
2089:.
2079:.
2067:.
2063:.
2039:.
2029:.
2017:.
2013:.
1989:.
1979:.
1969:15
1967:.
1963:.
1940:.
1930:.
1920:21
1918:.
1914:.
1891:.
1881:.
1871:.
1859:.
1855:.
1832:.
1822:.
1812:.
1800:.
1796:.
1773:.
1763:.
1755:.
1743:.
1739:.
1715:.
1705:.
1693:.
1689:.
1665:.
1655:.
1645:.
1633:.
1629:.
1606:.
1596:.
1584:.
1580:.
1557:.
1547:40
1545:.
1522:.
1510:15
1508:.
1504:.
1481:.
1471:.
1461:25
1459:.
1455:.
1432:.
1422:.
1414:.
1402:.
1398:.
1386:^
1372:.
1364:.
1352:.
1329:.
1321:.
1313:.
1301:.
1278:.
1268:.
1256:.
1252:.
1229:.
1219:.
1211:.
1199:.
1195:.
1172:.
1164:.
1156:.
1146:69
1144:.
1120:.
1110:.
1100:.
1088:.
1084:.
1061:.
1051:.
1041:.
1029:.
1025:.
1002:.
992:.
980:.
976:.
953:.
945:.
933:.
909:.
901:.
891:25
889:.
865:.
857:.
847:25
845:.
841:.
818:.
808:.
796:.
792:.
769:.
757:16
755:.
751:.
728:.
718:.
708:.
698:95
696:.
692:.
669:.
659:.
649:.
639:93
637:.
633:.
610:.
600:.
588:.
584:.
561:.
551:.
541:31
539:.
535:.
512:.
502:.
490:.
486:.
259:.
239:,
235:,
231:,
227:,
223:,
219:,
207:,
201:,
195:,
189:,
185:,
181:,
177:,
87:.
80:.
3124:.
3102::
3081:.
3059::
3038:.
3018::
3001:.
2979::
2948:.
2926::
2899:.
2877::
2847:.
2821:.
2801::
2777:.
2757::
2749::
2726:.
2706::
2698::
2675:.
2653::
2626:.
2604::
2577:.
2565::
2542:.
2520::
2493:.
2471::
2444:.
2422::
2414::
2408:4
2384:.
2362::
2356:8
2335:.
2313::
2286:.
2261:.
2237::
2229::
2202:.
2180::
2153:.
2131::
2097:.
2075::
2047:.
2025::
1997:.
1975::
1948:.
1926::
1899:.
1875::
1867::
1840:.
1816::
1808::
1802:6
1781:.
1759::
1751::
1723:.
1701::
1673:.
1649::
1641::
1614:.
1592::
1586:5
1565:.
1553::
1530:.
1516::
1489:.
1475::
1467::
1440:.
1418::
1410::
1380:.
1360::
1337:.
1317::
1309::
1286:.
1264::
1237:.
1215::
1207::
1180:.
1152::
1128:.
1104::
1096::
1069:.
1045::
1037::
1010:.
988::
961:.
941::
935:8
917:.
897::
873:.
853::
826:.
804::
777:.
763::
736:.
712::
704::
677:.
653::
645::
618:.
596::
569:.
547::
520:.
498::
492:5
141:.
41:(
20:)
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
