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Volumn 44, Issue 20, 2016, Pages 9555-9564

Guide RNA engineering for versatile Cas9 functionality

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 9; RNA; BACTERIAL PROTEIN; CAS9 ENDONUCLEASE STREPTOCOCCUS PYOGENES; ENDONUCLEASE; GUIDE RNA; PROTEIN BINDING;

EID: 85016109938     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gkw908     Document Type: Review
Times cited : (68)

References (94)
  • 1
    • 74249095519 scopus 로고    scopus 로고
    • CRISPR/Cas, the immune system of bacteria and archaea
    • Horvath,P. and Barrangou,R. (2010) CRISPR/Cas, the immune system of bacteria and archaea. Science, 327, 167-170.
    • (2010) Science , vol.327 , pp. 167-170
    • Horvath, P.1    Barrangou, R.2
  • 3
    • 39149142575 scopus 로고    scopus 로고
    • CRISPR - A widespread system that provides acquired resistance against phages in bacteria and archaea
    • Sorek,R., Kunin,V. and Hugenholtz,P. (2008) CRISPR - a widespread system that provides acquired resistance against phages in bacteria and archaea. Nat. Rev. Microbiol., 6, 181-186.
    • (2008) Nat. Rev. Microbiol. , vol.6 , pp. 181-186
    • Sorek, R.1    Kunin, V.2    Hugenholtz, P.3
  • 6
    • 0036267740 scopus 로고    scopus 로고
    • Identification of genes that are associated with DNA repeats in prokaryotes
    • Jansen,R., Embden,J.D.A. van, Gaastra,W. and Schouls,L.M. (2002) Identification of genes that are associated with DNA repeats in prokaryotes. Mol. Microbiol., 43, 1565-1575.
    • (2002) Mol. Microbiol. , vol.43 , pp. 1565-1575
    • Jansen, R.1    Van Embden, J.D.A.2    Gaastra, W.3    Schouls, L.M.4
  • 7
    • 84954285537 scopus 로고    scopus 로고
    • The Heroes of CRISPR
    • Lander,E.S. (2016) The Heroes of CRISPR. Cell, 164, 18-28.
    • (2016) Cell , vol.164 , pp. 18-28
    • Lander, E.S.1
  • 11
    • 84894081986 scopus 로고    scopus 로고
    • Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos
    • Niu,Y., Shen,B., Cui,Y., Chen,Y., Wang,J., Wang,L., Kang,Y., Zhao,X., Si,W., Li,W. et al. (2014) Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos. Cell, 156, 836-843.
    • (2014) Cell , vol.156 , pp. 836-843
    • Niu, Y.1    Shen, B.2    Cui, Y.3    Chen, Y.4    Wang, J.5    Wang, L.6    Kang, Y.7    Zhao, X.8    Si, W.9    Li, W.10
  • 12
    • 84897594300 scopus 로고    scopus 로고
    • One-step generation of knockout pigs by zygote injection of CRISPR/Cas system
    • Hai,T., Teng,F., Guo,R., Li,W. and Zhou,Q. (2014) One-step generation of knockout pigs by zygote injection of CRISPR/Cas system. Cell Res., 24, 372-375.
    • (2014) Cell Res. , vol.24 , pp. 372-375
    • Hai, T.1    Teng, F.2    Guo, R.3    Li, W.4    Zhou, Q.5
  • 14
    • 84958214080 scopus 로고    scopus 로고
    • Exploiting the CRISPR/Cas9 PAM Constraint for Single-Nucleotide Resolution Interventions
    • Li,Y., Mendiratta,S., Ehrhardt,K., Kashyap,N., White,M.A. and Bleris,L. (2016) Exploiting the CRISPR/Cas9 PAM Constraint for Single-Nucleotide Resolution Interventions. PLoS One, 11, e0144970.
    • (2016) PLoS One , vol.11
    • Li, Y.1    Mendiratta, S.2    Ehrhardt, K.3    Kashyap, N.4    White, M.A.5    Bleris, L.6
  • 16
    • 84876567971 scopus 로고    scopus 로고
    • RNA-programmed genome editing in human cells
    • Jinek,M., East,A., Cheng,A., Lin,S., Ma,E. and Doudna,J. (2013) RNA-programmed genome editing in human cells. Elife, 2, e00471.
    • (2013) Elife , vol.2 , pp. e00471
    • Jinek, M.1    East, A.2    Cheng, A.3    Lin, S.4    Ma, E.5    Doudna, J.6
  • 19
    • 23844505202 scopus 로고    scopus 로고
    • Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin
    • Bolotin,A., Quinquis,B., Sorokin,A. and Dusko Ehrlich,S. (2005) Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Microbiology, 151, 2551-2561.
    • (2005) Microbiology , vol.151 , pp. 2551-2561
    • Bolotin, A.1    Quinquis, B.2    Sorokin, A.3    Dusko Ehrlich, S.4
  • 20
    • 34248374277 scopus 로고    scopus 로고
    • A putative RNA-interference-based immune system in prokaryotes: Computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action
    • Makarova,K.S., Grishin,N. V, Shabalina,S.A., Wolf,Y.I., Koonin,E. V, Fire,A., Hannon,G., Cogoni,C., Macino,G., Bernstein,E. et al. (2006) A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action. Biol. Direct, 1, 7.
    • (2006) Biol. Direct , vol.1 , pp. 7
    • Makarova, K.S.1    Grishin, N.V.2    Shabalina, S.A.3    Wolf, Y.I.4    Koonin, E.V.5    Fire, A.6    Hannon, G.7    Cogoni, C.8    Macino, G.9    Bernstein, E.10
  • 22
    • 84866859751 scopus 로고    scopus 로고
    • Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria
    • Gasiunas,G., Barrangou,R., Horvath,P. and Siksnys,V. (2012) Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proc. Natl. Acad. Sci. U.S.A., 109, E2579-E2586.
    • (2012) Proc. Natl. Acad. Sci. U.S.A. , vol.109 , pp. E2579-E2586
    • Gasiunas, G.1    Barrangou, R.2    Horvath, P.3    Siksnys, V.4
  • 23
    • 84865070369 scopus 로고    scopus 로고
    • A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity
    • Jinek,M., Chylinski,K., Fonfara,I., Hauer,M., Doudna,J.A. and Charpentier,E. (2012) A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science, 337, 816-821.
    • (2012) Science , vol.337 , pp. 816-821
    • Jinek, M.1    Chylinski, K.2    Fonfara, I.3    Hauer, M.4    Doudna, J.A.5    Charpentier, E.6
  • 24
    • 75749118174 scopus 로고    scopus 로고
    • Self versus non-self discrimination during CRISPR RNA-directed immunity
    • Marraffini,L.A. and Sontheimer,E.J. (2010) Self versus non-self discrimination during CRISPR RNA-directed immunity. Nature, 463, 568-571.
    • (2010) Nature , vol.463 , pp. 568-571
    • Marraffini, L.A.1    Sontheimer, E.J.2
  • 25
    • 64049118040 scopus 로고    scopus 로고
    • Short motif sequences determine the targets of the prokaryotic CRISPR defence system
    • Mojica,F.J.M., Díez-Villaseñor,C., García-Martínez,J. and Almendros,C. (2009) Short motif sequences determine the targets of the prokaryotic CRISPR defence system. Microbiology, 155, 733-740.
    • (2009) Microbiology , vol.155 , pp. 733-740
    • Mojica, F.J.M.1    Díez-Villaseñor, C.2    García-Martínez, J.3    Almendros, C.4
  • 26
    • 84895871173 scopus 로고    scopus 로고
    • DNA interrogation by the CRISPR RNA-guided endonuclease Cas9
    • Sternberg,S.H., Redding,S., Jinek,M., Greene,E.C. and Doudna,J.A. (2014) DNA interrogation by the CRISPR RNA-guided endonuclease Cas9. Nature, 507, 62-67.
    • (2014) Nature , vol.507 , pp. 62-67
    • Sternberg, S.H.1    Redding, S.2    Jinek, M.3    Greene, E.C.4    Doudna, J.A.5
  • 29
    • 84946215320 scopus 로고    scopus 로고
    • Conformational control of DNA target cleavage by CRISPR-Cas9
    • Sternberg,S.H., LaFrance,B., Kaplan,M. and Doudna,J.A. (2015) Conformational control of DNA target cleavage by CRISPR-Cas9. Nature, 527, 110-113.
    • (2015) Nature , vol.527 , pp. 110-113
    • Sternberg, S.H.1    LaFrance, B.2    Kaplan, M.3    Doudna, J.A.4
  • 30
    • 84908508061 scopus 로고    scopus 로고
    • Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease
    • Anders,C., Niewoehner,O., Duerst,A. and Jinek,M. (2014) Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease. Nature, 513, 569-573.
    • (2014) Nature , vol.513 , pp. 569-573
    • Anders, C.1    Niewoehner, O.2    Duerst, A.3    Jinek, M.4
  • 38
    • 84960449403 scopus 로고    scopus 로고
    • The Neisseria meningitidis CRISPR-Cas9 system enables specific genome editing in mammalian cells
    • Lee,C.M., Cradick,T.J. and Bao,G. (2016) The Neisseria meningitidis CRISPR-Cas9 system enables specific genome editing in mammalian cells. Mol. Ther., 24, 645-654.
    • (2016) Mol. Ther. , vol.24 , pp. 645-654
    • Lee, C.M.1    Cradick, T.J.2    Bao, G.3
  • 44
  • 46
    • 84884160273 scopus 로고    scopus 로고
    • CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering
    • Mali,P., Aach,J., Stranges,P.B., Esvelt,K.M., Moosburner,M., Kosuri,S., Yang,L. and Church,G.M. (2013) CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nat. Biotechnol., 31, 833-838.
    • (2013) Nat. Biotechnol. , vol.31 , pp. 833-838
    • Mali, P.1    Aach, J.2    Stranges, P.B.3    Esvelt, K.M.4    Moosburner, M.5    Kosuri, S.6    Yang, L.7    Church, G.M.8
  • 51
    • 0025119137 scopus 로고
    • Monomethylated cap structures facilitate RNA export from the nucleus
    • Hamm,J. and Mattaj,I.W. (1990) Monomethylated cap structures facilitate RNA export from the nucleus. Cell, 63, 109-118.
    • (1990) Cell , vol.63 , pp. 109-118
    • Hamm, J.1    Mattaj, I.W.2
  • 53
    • 84907331721 scopus 로고    scopus 로고
    • Expansion of the CRISPR-Cas9 genome targeting space through the use of H1 promoter-expressed guide RNAs
    • Ranganathan,V., Wahlin,K., Maruotti,J. and Zack,D.J. (2014) Expansion of the CRISPR-Cas9 genome targeting space through the use of H1 promoter-expressed guide RNAs. Nat. Commun., 5, 4516.
    • (2014) Nat. Commun. , vol.5 , pp. 4516
    • Ranganathan, V.1    Wahlin, K.2    Maruotti, J.3    Zack, D.J.4
  • 54
    • 8844249359 scopus 로고    scopus 로고
    • Development of a tightly regulated U6 promoter for shRNA expression
    • Lin,X., Yang,J., Chen,J., Gunasekera,A., Fesik,S.W. and Shen,Y. (2004) Development of a tightly regulated U6 promoter for shRNA expression. FEBS Lett., 577, 376-380.
    • (2004) FEBS Lett. , vol.577 , pp. 376-380
    • Lin, X.1    Yang, J.2    Chen, J.3    Gunasekera, A.4    Fesik, S.W.5    Shen, Y.6
  • 55
    • 84924621296 scopus 로고    scopus 로고
    • An inducible lentiviral guide RNA platform enables the identification of tumor-essential genes and tumor-promoting mutations in vivo
    • Aubrey,B.J., Kelly,G.L., Kueh,A.J., Brennan,M.S., O'Connor,L., Milla,L., Wilcox,S., Tai,L., Strasser,A. and Herold,M.J. (2015) An inducible lentiviral guide RNA platform enables the identification of tumor-essential genes and tumor-promoting mutations in vivo. Cell Rep., 10, 1422-1432.
    • (2015) Cell Rep. , vol.10 , pp. 1422-1432
    • Aubrey, B.J.1    Kelly, G.L.2    Kueh, A.J.3    Brennan, M.S.4    O'Connor, L.5    Milla, L.6    Wilcox, S.7    Tai, L.8    Strasser, A.9    Herold, M.J.10
  • 57
    • 0036784630 scopus 로고    scopus 로고
    • In vivo kinetics of mRNA splicing and transport in mammalian cells
    • Audibert,A., Weil,D. and Dautry,F. (2002) In vivo kinetics of mRNA splicing and transport in mammalian cells. Mol. Cell. Biol., 22, 6706-6718.
    • (2002) Mol. Cell. Biol. , vol.22 , pp. 6706-6718
    • Audibert, A.1    Weil, D.2    Dautry, F.3
  • 58
    • 0033064680 scopus 로고    scopus 로고
    • The stability and fate of a spliced intron from vertebrate cells
    • Clement,J.Q., Qian,L., Kaplinsky,N. and Wilkinson,M.F. (1999) The stability and fate of a spliced intron from vertebrate cells. RNA, 5, 206-220.
    • (1999) RNA , vol.5 , pp. 206-220
    • Clement, J.Q.1    Qian, L.2    Kaplinsky, N.3    Wilkinson, M.F.4
  • 59
    • 84901195977 scopus 로고    scopus 로고
    • Multiplexed and programmable regulation of gene networks with an integrated RNA and CRISPR/Cas toolkit in human cells
    • Nissim,L., Perli,S.D., Fridkin,A., Perez-Pinera,P. and Lu,T.K. (2014) Multiplexed and programmable regulation of gene networks with an integrated RNA and CRISPR/Cas toolkit in human cells. Mol. Cell, 54, 698-710.
    • (2014) Mol. Cell , vol.54 , pp. 698-710
    • Nissim, L.1    Perli, S.D.2    Fridkin, A.3    Perez-Pinera, P.4    Lu, T.K.5
  • 60
    • 84862190458 scopus 로고    scopus 로고
    • Csy4 relies on an unusual catalytic dyad to position and cleave CRISPR RNA
    • Haurwitz,R.E., Sternberg,S.H. and Doudna,J.A. (2012) Csy4 relies on an unusual catalytic dyad to position and cleave CRISPR RNA. EMBO J., 31, 2824-2832.
    • (2012) EMBO J. , vol.31 , pp. 2824-2832
    • Haurwitz, R.E.1    Sternberg, S.H.2    Doudna, J.A.3
  • 61
    • 84858659496 scopus 로고    scopus 로고
    • Mechanism of substrate selection by a highly specific CRISPR endoribonuclease
    • Sternberg,S.H., Haurwitz,R.E. and Doudna,J.A. (2012) Mechanism of substrate selection by a highly specific CRISPR endoribonuclease. RNA, 18, 661-672.
    • (2012) RNA , vol.18 , pp. 661-672
    • Sternberg, S.H.1    Haurwitz, R.E.2    Doudna, J.A.3
  • 63
    • 84868519473 scopus 로고    scopus 로고
    • A triple helix stabilizes the 3′ ends of long noncoding RNAs that lack poly(A) tails
    • Wilusz,J.E., JnBaptiste,C.K., Lu,L.Y., Kuhn,C.-D., Joshua-Tor,L. and Sharp,P.A. (2012) A triple helix stabilizes the 3′ ends of long noncoding RNAs that lack poly(A) tails. Genes Dev., 26, 2392-2407.
    • (2012) Genes Dev. , vol.26 , pp. 2392-2407
    • Wilusz, J.E.1    JnBaptiste, C.K.2    Lu, L.Y.3    Kuhn, C.-D.4    Joshua-Tor, L.5    Sharp, P.A.6
  • 64
    • 84897546295 scopus 로고    scopus 로고
    • Self-processing of ribozyme-flanked RNAs into guide RNAs in vitro and in vivo for CRISPR-mediated genome editing
    • Gao,Y. and Zhao,Y. (2014) Self-processing of ribozyme-flanked RNAs into guide RNAs in vitro and in vivo for CRISPR-mediated genome editing. J. Integr. Plant Biol., 56, 343-349.
    • (2014) J. Integr. Plant Biol. , vol.56 , pp. 343-349
    • Gao, Y.1    Zhao, Y.2
  • 65
    • 84925262435 scopus 로고    scopus 로고
    • Boosting CRISPR/Cas9 multiplex editing capability with the endogenous tRNA-processing system
    • Xie,K., Minkenberg,B. and Yang,Y. (2015) Boosting CRISPR/Cas9 multiplex editing capability with the endogenous tRNA-processing system. Proc. Natl. Acad. Sci. U.S.A., 112, 3570-3575.
    • (2015) Proc. Natl. Acad. Sci. U.S.A. , vol.112 , pp. 3570-3575
    • Xie, K.1    Minkenberg, B.2    Yang, Y.3
  • 66
    • 0023651444 scopus 로고
    • Oligoribonucleotide synthesis using T7 RNA polymerase and synthetic DNA templates
    • Milligan,J.F., Groebe,D.R., Witherell,G.W. and Uhlenbeck,O.C. (1987) Oligoribonucleotide synthesis using T7 RNA polymerase and synthetic DNA templates. Nucleic Acids Res., 15, 8783-8798.
    • (1987) Nucleic Acids Res. , vol.15 , pp. 8783-8798
    • Milligan, J.F.1    Groebe, D.R.2    Witherell, G.W.3    Uhlenbeck, O.C.4
  • 68
    • 84990068709 scopus 로고    scopus 로고
    • Electroporation of Cas9 protein/sgRNA into early pronuclear zygotes generates non-mosaic mutants in the mouse
    • Hashimoto,M., Yamashita,Y. and Takemoto,T. (2016) Electroporation of Cas9 protein/sgRNA into early pronuclear zygotes generates non-mosaic mutants in the mouse.Dev. Biol., 418, 1-9.
    • (2016) Dev. Biol. , vol.418 , pp. 1-9
    • Hashimoto, M.1    Yamashita, Y.2    Takemoto, T.3
  • 71
    • 84969916200 scopus 로고    scopus 로고
    • Long-term dual-color tracking of genomic loci by modified sgRNAs of the CRISPR/Cas9 system
    • Shao,S., Zhang,W., Hu,H., Xue,B., Qin,J., Sun,C., Sun,Y., Wei,W. and Sun,Y. (2016) Long-term dual-color tracking of genomic loci by modified sgRNAs of the CRISPR/Cas9 system. Nucleic Acids Res., 44, e86.
    • (2016) Nucleic Acids Res. , vol.44 , pp. e86
    • Shao, S.1    Zhang, W.2    Hu, H.3    Xue, B.4    Qin, J.5    Sun, C.6    Sun, Y.7    Wei, W.8    Sun, Y.9
  • 72
    • 84966908028 scopus 로고    scopus 로고
    • Multiplexed labeling of genomic loci with dCas9 and engineered sgRNAs using CRISPRainbow
    • Ma,H., Tu,L.-C., Naseri,A., Huisman,M., Zhang,S., Grunwald,D. and Pederson,T. (2016) Multiplexed labeling of genomic loci with dCas9 and engineered sgRNAs using CRISPRainbow. Nat. Biotechnol., 34, 528-530.
    • (2016) Nat. Biotechnol. , vol.34 , pp. 528-530
    • Ma, H.1    Tu, L.-C.2    Naseri, A.3    Huisman, M.4    Zhang, S.5    Grunwald, D.6    Pederson, T.7
  • 73
    • 84892749369 scopus 로고    scopus 로고
    • Genetic screens in human cells using the CRISPR-Cas9 system
    • Wang,T., Wei,J.J., Sabatini,D.M. and Lander,E.S. (2014) Genetic screens in human cells using the CRISPR-Cas9 system. Science, 343, 80-84.
    • (2014) Science , vol.343 , pp. 80-84
    • Wang, T.1    Wei, J.J.2    Sabatini, D.M.3    Lander, E.S.4
  • 75
    • 84898665052 scopus 로고    scopus 로고
    • Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library
    • Koike-Yusa,H., Li,Y., Tan,E.-P., Velasco-Herrera,M.D.C. and Yusa,K. (2013) Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library. Nat. Biotechnol., 32, 267-273.
    • (2013) Nat. Biotechnol. , vol.32 , pp. 267-273
    • Koike-Yusa, H.1    Li, Y.2    Tan, E.-P.3    Velasco-Herrera, M.D.C.4    Yusa, K.5
  • 81
    • 84896929630 scopus 로고    scopus 로고
    • Improving CRISPR-Cas nuclease specificity using truncated guide RNAs
    • Fu,Y., Sander,J.D., Reyon,D., Cascio,V.M. and Joung,J.K. (2014) Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat. Biotechnol., 32, 279-284.
    • (2014) Nat. Biotechnol. , vol.32 , pp. 279-284
    • Fu, Y.1    Sander, J.D.2    Reyon, D.3    Cascio, V.M.4    Joung, J.K.5
  • 84
    • 84934267574 scopus 로고    scopus 로고
    • Multiplexable, locus-specific targeting of long RNAs with CRISPR-Display
    • Shechner,D.M., Hacisuleyman,E., Younger,S.T. and Rinn,J.L. (2015) Multiplexable, locus-specific targeting of long RNAs with CRISPR-Display. Nat. Methods, 12, 664-670.
    • (2015) Nat. Methods , vol.12 , pp. 664-670
    • Shechner, D.M.1    Hacisuleyman, E.2    Younger, S.T.3    Rinn, J.L.4
  • 88
    • 0027404265 scopus 로고
    • The RNA binding site of bacteriophage MS2 coat protein
    • Peabody,D.S. (1993) The RNA binding site of bacteriophage MS2 coat protein. EMBO J., 12, 595-600.
    • (1993) EMBO J. , vol.12 , pp. 595-600
    • Peabody, D.S.1
  • 93
    • 0032242421 scopus 로고    scopus 로고
    • The limits of specificity: An experimental analysis with RNA aptamers to MS2 coat protein variants
    • Hirao,I., Spingola,M., Peabody,D. and Ellington,A.D. (1999) The limits of specificity: an experimental analysis with RNA aptamers to MS2 coat protein variants. Mol. Divers., 4, 75-89.
    • (1999) Mol. Divers. , vol.4 , pp. 75-89
    • Hirao, I.1    Spingola, M.2    Peabody, D.3    Ellington, A.D.4
  • 94
    • 84883785822 scopus 로고    scopus 로고
    • Multiplex and homologous recombination-mediated genome editing in Arabidopsis and Nicotiana benthamiana using guide RNA and Cas9
    • Li,J.-F., Norville,J.E., Aach,J., McCormack,M., Zhang,D., Bush,J., Church,G.M. and Sheen,J. (2013) Multiplex and homologous recombination-mediated genome editing in Arabidopsis and Nicotiana benthamiana using guide RNA and Cas9. Nat. Biotechnol., 31, 688-691.
    • (2013) Nat. Biotechnol. , vol.31 , pp. 688-691
    • Li, J.-F.1    Norville, J.E.2    Aach, J.3    McCormack, M.4    Zhang, D.5    Bush, J.6    Church, G.M.7    Sheen, J.8


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