Open Access

Genome editing: A perspective on the application of CRISPR/Cas9 to study human diseases (Review)

  • Authors:
    • Diana Raquel Rodríguez‑Rodríguez
    • Ramiro Ramírez‑Solís
    • Mario Alberto Garza‑Elizondo
    • María De Lourdes Garza‑Rodríguez
    • Hugo Alberto Barrera‑Saldaña
  • View Affiliations

  • Published online on: February 26, 2019     https://doi.org/10.3892/ijmm.2019.4112
  • Pages: 1559-1574
  • Copyright: © Rodríguez‑Rodríguez et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Genome editing reemerged in 2012 with the development of CRISPR/Cas9 technology, which is a genetic manipulation tool derived from the defense system of certain bacteria against viruses and plasmids. This method is easy to apply and has been used in a wide variety of experimental models, including cell lines, laboratory animals, plants, and even in human clinical trials. The CRISPR/Cas9 system consists of directing the Cas9 nuclease to create a site‑directed double‑strand DNA break using a small RNA molecule as a guide. A process that allows a permanent modification of the genomic target sequence can repair the damage caused to DNA. In the present study, the basic principles of the CRISPR/Cas9 system are reviewed, as well as the strategies and modifications of the enzyme Cas9 to eliminate the off‑target cuts, and the different applications of CRISPR/Cas9 as a system for visualization and gene expression activation or suppression. In addition, the review emphasizes on the potential application of this system in the treatment of different diseases, such as pulmonary, gastrointestinal, hematologic, immune system, viral, autoimmune and inflammatory diseases, and cancer.

References

1 

Im W, Moon J and Kim M: Applications of CRISPR/Cas9 for gene editing in hereditary movement disorders. J Mov Disord. 9:136–143. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Gaj T, Gersbach CA and Barbas CF III: ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol. 31:397–405. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Sander JD and Joung JK: CRISPR-Cas systems for editing, regulating and targeting genomes. Nat Biotechnol. 32:347–355. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Cox DBT, Platt RJ and Zhang F: Therapeutic genome editing: Prospects and challenges. Nat Med. 21:121–131. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Epinat JC, Arnould S, Chames P, Rochaix P, Desfontaines D, Puzin C, Patin A, Zanghellini A, Pâques F and Lacroix E: A novel engineered meganuclease induces homologous recombination in yeast and mammalian cells. Nucleic Acids Res. 31:2952–2962. 2003. View Article : Google Scholar : PubMed/NCBI

6 

Urnov FD, Rebar EJ, Holmes MC, Zhang HS and Gregory PD: Genome editing with engineered zinc finger nucleases. Nat Rev Genet. 11:636–646. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Miller JC, Tan S, Qiao G, Barlow KA, Wang J, Xia DF, Meng X, Paschon DE, Leung E, Hinkley SJ, et al: A TALE nuclease architecture for efficient genome editing. Nat Biotechnol. 29:143–148. 2011. View Article : Google Scholar

8 

Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA and Charpentier E: A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science. 337:816–821. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Horvath P and Barrangou R: CRISPR/Cas, the immune system of bacteria and archaea. Science. 327:167–170. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Sorek R, Kunin V and Hugenholtz P: CRISPR-a widespread system that provides acquired resistance against phages in bacteria and archaea. Nat Rev Microbiol. 6:181–186. 2008. View Article : Google Scholar

11 

Singh V, Braddick D and Dhar PK: Exploring the potential of genome editing CRISPR-Cas9 technology. Gene. 599:1–18. 2017. View Article : Google Scholar

12 

Makarova KS, Wolf YI, Alkhnbashi OS, Costa F, Shah SA, Saunders SJ, Barrangou R, Brouns SJ, Charpentier E, Haft DH, et al: An updated evolutionary classification of CRISPR-Cas systems. Nat Rev Microbiol. 13:722–736. 2015. View Article : Google Scholar

13 

Mojica FJ, Ferrer C, Juez G and Rodríguez-Valera F: Long stretches of short tandem repeats are present in the largest replicons of the Archaea Haloferax mediterranei and Haloferax volcanii and could be involved in replicon partitioning. Mol Microbiol. 17:85–93. 1995. View Article : Google Scholar : PubMed/NCBI

14 

Riehle MM, Bennett AF and Long AD: Genetic architecture of thermal adaptation in Escherichia coli. Proc Natl Acad Sci USA. 98:525–530. 2001. View Article : Google Scholar : PubMed/NCBI

15 

DeBoy RT, Mongodin EF, Emerson JB and Nelson KE: Chromosome evolution in the Thermotogales: Large-scale inversions and strain diversification of CRISPR sequences. J Bacteriol. 188:2364–2374. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Makarova KS, Aravind L, Grishin NV, Rogozin IB and Koonin EV: A DNA repair system specific for thermophilic Archaea and bacteria predicted by genomic context analysis. Nucleic Acids Res. 30:482–496. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Ishino Y, Shinagawa H, Makino K, Amemura M and Nakata A: Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J Bacteriol. 169:5429–5433. 1987. View Article : Google Scholar : PubMed/NCBI

18 

Mojica FJ, Díez-Villaseñor C, Soria E and Juez G: Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria. Mol Microbiol. 36:244–246. 2000. View Article : Google Scholar : PubMed/NCBI

19 

Jansen R, Embden JD, Gaastra W and Schouls LM: Identification of genes that are associated with DNA repeats in prokaryotes. Mol Microbiol. 43:1565–1575. 2002. View Article : Google Scholar : PubMed/NCBI

20 

Mojica FJ, Díez-Villaseñor C, García-Martínez J and Soria E: Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J Mol Evol. 60:174–182. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Bolotin A, Quinquis B, Sorokin A and Ehrlich SD: Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Microbiology. 151:2551–2561. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Pourcel C, Salvignol G and Vergnaud G: CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies. Microbiology. 151:653–663. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, Romero DA and Horvath P: CRISPR provides acquired resistance against viruses in prokaryotes. Science. 315:1709–1712. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Brouns SJJ, Jore MM, Lundgren M, Westra ER, Slijkhuis RJH, Snijders APL, Dickman MJ, Makarova KS, Koonin EV and van der Oost J: Small CRISPR RNAs guide antiviral defense in prokaryotes. Science. 321:960–964. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Garneau JE, Dupuis MÈ, Villion M, Romero DA, Barrangou R, Boyaval P, Fremaux C, Horvath P, Magadán AH and Moineau S: The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Nature. 468:67–71. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Deltcheva E, Chylinski K, Sharma CM, Gonzales K, Chao Y, Pirzada ZA, Eckert MR, Vogel J and Charpentier E: CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature. 471:602–607. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Sapranauskas R, Gasiunas G, Fremaux C, Barrangou R, Horvath P and Siksnys V: The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli. Nucleic Acids Res. 39:9275–9282. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, Norville JE and Church GM: RNA-guided human genome engineering via Cas9. Science. 339:823–826. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA and Zhang F: Multiplex genome engineering using CRISPR/Cas systems. Science. 339:819–823. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Cornu TI, Mussolino C and Cathomen T: Refining strategies to translate genome editing to the clinic. Nat Med. 23:415–423. 2017. View Article : Google Scholar : PubMed/NCBI

31 

Cyranoski D: CRISPR gene-editing tested in a person for the first time. Nature. 539:479. 2016. View Article : Google Scholar : PubMed/NCBI

32 

Cyranoski D: Chinese scientists to pioneer first human CRISPR trial. Nature. 535:476–477. 2016. View Article : Google Scholar : PubMed/NCBI

33 

Shub DA, Goodrich-Blair H and Eddy SR: Amino-acid-sequence motif of group I intron endonucleases is conserved in open reading frames of group II introns. Trends Biochem Sci. 19:402–404. 1994. View Article : Google Scholar : PubMed/NCBI

34 

Al-Attar S, Westra ER, van der Oost J and Brouns SJ: Clustered regularly interspaced short palindromic repeats (CRISPRs): The hallmark of an ingenious antiviral defense mechanism in prokaryotes. Biol Chem. 392:277–289. 2011. View Article : Google Scholar : PubMed/NCBI

35 

Wright AV, Nuñez JK and Doudna JA: Biology and applications of CRISPR systems: Harnessing nature’s toolbox for genome engineering. Cell. 164:29–44. 2016. View Article : Google Scholar : PubMed/NCBI

36 

Zhang F, Wen Y and Guo X: CRISPR/Cas9 for genome editing: Progress implications and challenges. Hum Mol Genet. 23:R40–R46. 2014. View Article : Google Scholar : PubMed/NCBI

37 

Canver MC, Bauer DE and Orkin SH: Functional interrogation of non-coding DNA through CRISPR genome editing. Methods. 121–122. 118–129. 2017.

38 

Karvelis T, Gasiunas G, Miksys A, Barrangou R, Horvath P and Siksnys V: crRNA and tracrRNA guide Cas9-mediated DNA interference in Streptococcus thermophilus. RNA Biol. 10:841–851. 2013. View Article : Google Scholar : PubMed/NCBI

39 

Gasiunas G, Barrangou R, Horvath P and Siksnys V: Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proc Natl Acad Sci USA. 109:E2579–E2586. 2012. View Article : Google Scholar : PubMed/NCBI

40 

Friedland AE, Baral R, Singhal P, Loveluck K, Shen S, Sanchez M, Marco E, Gotta GM, Maeder ML, Kennedy EM, et al: Characterization of Staphylococcus aureus Cas9: A smaller Cas9 for all-in-one adeno-associated virus delivery and paired nickase applications. Genome Biol. 16:2572015. View Article : Google Scholar : PubMed/NCBI

41 

Ran FA, Cong L, Yan WX, Scott DA, Gootenberg JS, Kriz AJ, Zetsche B, Shalem O, Wu X, Makarova KS, et al: In vivo genome editing using Staphylococcus aureus Cas9. Nature. 520:186–191. 2015. View Article : Google Scholar : PubMed/NCBI

42 

Hou Z, Zhang Y, Propson NE, Howden SE, Chu LF, Sontheimer EJ and Thomson JA: Efficient genome engineering in human pluripotent stem cells using Cas9 from Neisseria meningitidis. Proc Natl Acad Sci USA. 110:15644–15649. 2013. View Article : Google Scholar : PubMed/NCBI

43 

Chen F, Ding X, Feng Y, Seebeck T, Jiang Y and Davis GD: Targeted activation of diverse CRISPR-Cas systems for mammalian genome editing via proximal CRISPR targeting. Nat Commun. 8:149582017. View Article : Google Scholar : PubMed/NCBI

44 

Price AA, Sampson TR, Ratner HK, Grakoui A and Weiss DS: Cas9-mediated targeting of viral RNA in eukaryotic cells. Proc Natl Acad Sci USA. 112:6164–6169. 2015. View Article : Google Scholar : PubMed/NCBI

45 

Murovec J, Pirc Ž and Yang B: New variants of CRISPR RNA-guided genome editing enzymes. Plant Biotechnol J. 15:917–926. 2017. View Article : Google Scholar : PubMed/NCBI

46 

Oliveros JC, Franch M, Tabas-Madrid D, San-León D, Montoliu L, Cubas P and Pazos F: Breaking-Cas-interactive design of guide RNAs for CRISPR-Cas experiments for ENSEMBL genomes. Nucleic Acids Res. 44:W267–W271. 2016. View Article : Google Scholar : PubMed/NCBI

47 

Kaur K, Gupta AK, Rajput A and Kumar M: ge-CRISPR-an integrated pipeline for the prediction and analysis of sgRNAs genome editing efficiency for CRISPR/Cas system. Sci Rep. 6:308702016. View Article : Google Scholar

48 

Naito Y, Hino K, Bono H and Ui-Tei K: CRISPRdirect: Software for designing CRISPR/Cas guide RNA with reduced off-target sites. Bioinformatics. 31:1120–1123. 2015. View Article : Google Scholar :

49 

Heigwer F, Kerr G and Boutros M: E-CRISP: Fast CRISPR target site identification. Nat Methods. 11:122–123. 2014. View Article : Google Scholar : PubMed/NCBI

50 

Wong N, Liu W and Wang X: WU-CRISPR: Characteristics of functional guide RNAs for the CRISPR/Cas9 system. Genome Biol. 16:2182015. View Article : Google Scholar : PubMed/NCBI

51 

Doench JG, Hartenian E, Graham DB, Tothova Z, Hegde M, Smith I, Sullender M, Ebert BL, Xavier RJ and Root DE: Rational design of highly active sgRNAs for CRISPR-Cas9-mediated gene inactivation. Nat Biotechnol. 32:1262–1267. 2014. View Article : Google Scholar : PubMed/NCBI

52 

Chari R, Mali P, Moosburner M and Church GM: Unraveling CRISPR-Cas9 genome engineering parameters via a library-on-library approach. Nat Methods. 12:823–826. 2015. View Article : Google Scholar : PubMed/NCBI

53 

Chari R, Yeo NC, Chavez A and Church GM: sgRNA scorer 2.0: A species-independent model to predict CRISPR/Cas9 activity. ACS Synth Biol. 6:902–904. 2017. View Article : Google Scholar : PubMed/NCBI

54 

Moreno-Mateos MA, Vejnar CE, Beaudoin JD, Fernandez JP, Mis EK, Khokha MK and Giraldez AJ: CRISPRscan: Designing highly efficient sgRNAs for CRISPR-Cas9 targeting in vivo. Nat Methods. 12:982–988. 2015. View Article : Google Scholar : PubMed/NCBI

55 

Liu H, Wei Z, Dominguez A, Li Y, Wang X and Qi LS: CRISPR-ERA: A comprehensive design tool for CRISPR-mediated gene editing, repression and activation. Bioinformatics. 31:3676–3678. 2015. View Article : Google Scholar : PubMed/NCBI

56 

Stemmer M, Thumberger T, Del Sol, Keyer M, Wittbrodt J and Mateo JL: CCTop: An intuitive, flexible and reliable CRISPR/Cas9 target prediction tool. PLoS One. 10:e01246332015. View Article : Google Scholar : PubMed/NCBI

57 

Haeussler M, Schönig K, Eckert H, Eschstruth A, Mianné J, Renaud JB, Schneider-Maunoury S, Shkumatava A, Teboul L, Kent J, et al: Evaluation of off-target and on-target scoring algorithms and integration into the guide RNA selection tool CRISPOR. Genome Biol. 17:1482016. View Article : Google Scholar : PubMed/NCBI

58 

Montague TG, Cruz JM, Gagnon JA, Church GM and Valen E: CHOPCHOP: A CRISPR/Cas9 and TALEN web tool for genome editing. Nucleic Acids Res. 42:W401–W407. 2014. View Article : Google Scholar : PubMed/NCBI

59 

Prykhozhij SV, Rajan V, Gaston D and Berman JN: CRISPR multitargeter: A web tool to find common and unique CRISPR single guide RNA targets in a set of similar sequences. PLoS One. 10:e01193722015. View Article : Google Scholar : PubMed/NCBI

60 

O’Brien A and Bailey TL: GT-Scan: Identifying unique genomic targets. Bioinformatics. 30:2673–2675. 2014. View Article : Google Scholar :

61 

Hsu PD, Scott DA, Weinstein JA, Ran FA, Konermann S, Agarwala V, Li Y, Fine EJ, Wu X, Shalem O, et al: DNA targeting specificity of RNA-guided Cas9 nucleases. Nat Biotechnol. 31:827–832. 2013. View Article : Google Scholar : PubMed/NCBI

62 

Park J, Bae S and Kim JS: Cas-Designer: A web-based tool for choice of CRISPR-Cas9 target sites. Bioinformatics. 31:4014–4016. 2015.PubMed/NCBI

63 

Bae S, Park J and Kim JS: Cas-OFFinder: A fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA-guided endonucleases. Bioinformatics. 30:1473–1475. 2014. View Article : Google Scholar : PubMed/NCBI

64 

Cradick TJ, Qiu P, Lee CM, Fine EJ and Bao G: COSMID: A web-based tool for identifying and validating CRISPR/Cas off-target sites. Mol Ther Nucleic Acids. 3:e2142014. View Article : Google Scholar : PubMed/NCBI

65 

Hough SH, Kancleris K, Brody L, Humphryes-Kirilov N, Wolanski J, Dunaway K, Ajetunmobi A and Dillard V: Guide Picker is a comprehensive design tool for visualizing and selecting guides for CRISPR experiments. BMC Bioinformatics. 18:1672017. View Article : Google Scholar : PubMed/NCBI

66 

Güell M, Yang L and Church GM: Genome editing assessment using CRISPR genome analyzer (CRISPR-GA). Bioinformatics. 30:2968–2970. 2014. View Article : Google Scholar : PubMed/NCBI

67 

Cao J, Wu L, Zhang SM, Lu M, Cheung WK, Cai W, Gale M, Xu Q and Yan Q: An easy and efficient inducible CRISPR/Cas9 platform with improved specificity for multiple gene targeting. Nucleic Acids Res. 44:e1492016.PubMed/NCBI

68 

Ran FA, Hsu PD, Lin CY, Gootenberg JS, Konermann S, Trevino AE, Scott DA, Inoue A, Matoba S, Zhang Y and Zhang F: Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell. 154:1380–1389. 2013. View Article : Google Scholar : PubMed/NCBI

69 

Sato T, Sakuma T, Yokonishi T, Katagiri K, Kamimura S, Ogonuki N, Ogura A, Yamamoto T and Ogawa T: Genome editing in mouse spermatogonial stem cell lines Using TALEN and double-nicking CRISPR/Cas9. Stem Cell Reports. 5:75–82. 2015. View Article : Google Scholar : PubMed/NCBI

70 

Sakuma T, Masaki K, Abe-Chayama H, Mochida K, Yamamoto T and Chayama K: Highly multiplexed CRISPR-Cas9-nuclease and Cas9-nickase vectors for inactivation of hepatitis B virus. Genes Cells. 21:1253–1262. 2016. View Article : Google Scholar : PubMed/NCBI

71 

Slaymaker IM, Gao L, Zetsche B, Scott DA, Yan WX and Zhang F: Rationally engineered Cas9 nucleases with improved specificity. Science. 351:84–88. 2016. View Article : Google Scholar :

72 

Tsai SQ, Wyvekens N, Khayter C, Foden JA, Thapar V, Reyon D, Goodwin MJ, Aryee MJ and Joung JK: Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing. Nat Biotechnol. 32:569–576. 2014. View Article : Google Scholar : PubMed/NCBI

73 

Zhang H, Yan Z, Li M, Peabody M and He TC: CRISPR clear? Dimeric Cas9-Fok1 nucleases improve genome-editing specificity. Genes Dis. 1:6–7. 2014. View Article : Google Scholar : PubMed/NCBI

74 

Guilinger JP, Thompson DB and Liu DR: Fusion of catalytically inactive Cas9 to FokI nuclease improves the specificity of genome modification. Nat Biotechnol. 32:577–582. 2014. View Article : Google Scholar : PubMed/NCBI

75 

Wright AV, Sternberg SH, Taylor DW, Staahl BT, Bardales JA, Kornfeld JE and Doudna JA: Rational design of a split-Cas9 enzyme complex. Proc Natl Acad Sci USA. 112:2984–2989. 2015. View Article : Google Scholar : PubMed/NCBI

76 

Chew WL, Tabebordbar M, Cheng JK, Mali P, Wu EY, Ng AH, Zhu K, Wagers AJ and Church GM: A multifunctional AAV-CRISPR-Cas9 and its host response. Nat Methods. 13:868–874. 2016. View Article : Google Scholar : PubMed/NCBI

77 

Komor AC, Kim YB, Packer MS, Zuris JA and Liu DR: Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature. 533:420–424. 2016. View Article : Google Scholar : PubMed/NCBI

78 

Murugan K, Babu K, Sundaresan R, Rajan R and Sashital DG: The revolution continues: Newly discovered systems expand the CRISPR-Cas toolkit. Mol Cell. 68:15–25. 2017. View Article : Google Scholar : PubMed/NCBI

79 

Shmakov S, Abudayyeh OO, Makarova KS, Wolf YI, Gootenberg JS, Semenova E, Minakhin L, Joung J, Konermann S, Severinov K, et al: Discovery and functional characterization of diverse class 2 CRISPR-Cas systems. Mol Cell. 60:385–397. 2015. View Article : Google Scholar : PubMed/NCBI

80 

Abudayyeh OO, Gootenberg JS, Konermann S, Joung J, Slaymaker IM, Cox DB, Shmakov S, Makarova KS, Semenova E, Minakhin L, et al: C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector. Science. 353:aaf55732016. View Article : Google Scholar : PubMed/NCBI

81 

Abudayyeh OO, Gootenberg JS, Essletzbichler P, Han S, Joung J, Belanto JJ, Verdine V, Cox DBT, Kellner MJ, Regev A, et al: RNA targeting with CRISPR-Cas13. Nature. 550:280–284. 2017. View Article : Google Scholar : PubMed/NCBI

82 

Cox DBT, Gootenberg JS, Abudayyeh OO, Franklin B, Kellner MJ, Joung J and Zhang F: RNA editing with CRISPR-Cas13. Science. 358:1019–1027. 2017. View Article : Google Scholar : PubMed/NCBI

83 

Balboa D, Weltner J, Eurola S, Trokovic R, Wartiovaara K and Otonkoski T: Conditionally stabilized dCas9 activator for controlling gene expression in human cell reprogramming and differentiation. Stem Cell Reports. 5:448–459. 2015. View Article : Google Scholar : PubMed/NCBI

84 

Konermann S, Brigham MD, Trevino AE, Joung J, Abudayyeh OO, Barcena C, Hsu PD, Habib N, Gootenberg JS, Nishimasu H, et al: Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature. 517:583–588. 2015. View Article : Google Scholar :

85 

Piatek A, Ali Z, Baazim H, Li L, Abulfaraj A, Al-Shareef S, Aouida M and Mahfouz MM: RNA-guided transcriptional regulation in planta via synthetic dCas9-based transcription factors. Plant Biotechnol J. 13:578–589. 2015. View Article : Google Scholar

86 

Fu Y, Rocha PP, Luo VM, Raviram R, Deng Y, Mazzoni EO and Skok JA: CRISPR-dCas9 and sgRNA scaffolds enable dual-colour live imaging of satellite sequences and repeat-enriched individual loci. Nat Commun. 7:117072016. View Article : Google Scholar :

87 

Qin P, Parlak M, Kuscu C, Bandaria J, Mir M, Szlachta K, Singh R, Darzacq X, Yildiz A and Adli M: Live cell imaging of low- and non-repetitive chromosome loci using CRISPR-Cas9. Nat Commun. 8:147252017. View Article : Google Scholar : PubMed/NCBI

88 

Pankowicz FP, Barzi M, Legras X, Hubert L, Mi T, Tomolonis JA, Ravishankar M, Sun Q, Yang D, Borowiak M, et al: Reprogramming metabolic pathways in vivo with CRISPR/Cas9 genome editing to treat hereditary tyrosinaemia. Nat Commun. 7:126422016. View Article : Google Scholar : PubMed/NCBI

89 

Kang H, Minder P, Park MA, Mesquitta WT, Torbett BE and Slukvin II: CCR5 disruption in induced pluripotent stem cells using CRISPR/Cas9 provides selective resistance of immune cells to CCR5-tropic HIV-1 virus. Mol Ther Nucleic Acids. 4:e2682015. View Article : Google Scholar : PubMed/NCBI

90 

Brunger JM, Zutshi A, Willard VP, Gersbach CA and Guilak F: Genome engineering of stem cells for autonomously regulated, closed-loop delivery of biologic drugs. Stem Cell Reports. 8:1202–1213. 2017. View Article : Google Scholar : PubMed/NCBI

91 

Lin SR, Yang HC, Kuo YT, Liu CJ, Yang TY, Sung KC, Lin YY, Wang HY, Wang CC, Shen YC, et al: The CRISPR/Cas9 system facilitates clearance of the intrahepatic HBV templates in vivo. Mol Ther Nucleic Acids. 3:e1862014. View Article : Google Scholar : PubMed/NCBI

92 

Zhen S, Hua L, Takahashi Y, Narita S, Liu YH and Li Y: In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by CRISPR/Cas9. Biochem Biophys Res Commun. 450:1422–1426. 2014. View Article : Google Scholar : PubMed/NCBI

93 

Zhen S, Lu JJ, Wang LJ, Sun XM, Zhang JQ, Li X, Luo WJ and Zhao L: In vitro and in vivo synergistic therapeutic effect of cisplatin with human papillomavirus16 E6/E7 CRISPR/Cas9 on cervical cancer cell line. Transl Oncol. 9:498–504. 2016. View Article : Google Scholar : PubMed/NCBI

94 

Das D, Smith N, Wang X and Morgan IM: The deacetylase SIRT1 regulates the replication properties of human papilloma-virus 16 E1 and E2. J Virol. 91:e00102-e001172017. View Article : Google Scholar

95 

Merling R, Kuhns D, Sweeney C, Wu X, Burkett S, Chu J, Lee J, Koontz S, Di Pasquale G, Afione S, et al: Gene-edited pseudogene resurrection corrects p47 phox-deficient chronic granulomatous disease. Blood Adv. 1:270–278. 2016. View Article : Google Scholar

96 

Paquet D, Kwart D, Chen A, Sproul A, Jacob S, Teo S, Olsen KM, Gregg A, Noggle S and Tessier-Lavigne M: Efficient introduction of specific homozygous and heterozygous mutations using CRISPR/Cas9. Nature. 533:125–129. 2016. View Article : Google Scholar : PubMed/NCBI

97 

Schwank G, Koo BK, Sasselli V, Dekkers JF, Heo I, Demircan T, Sasaki N, Boymans S, Cuppen E, van der Ent CK, et al: Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell. 13:653–658. 2013. View Article : Google Scholar : PubMed/NCBI

98 

Yin H, Xue W, Chen S, Bogorad RL, Benedetti E, Grompe M, Koteliansky V, Sharp PA, Jacks T and Anderson DG: Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype. Nat Biotechnol. 32:551–553. 2014. View Article : Google Scholar : PubMed/NCBI

99 

Gui H, Schriemer D, Cheng WW, Chauhan RK, Antiňolo G, Berrios C, Bleda M, Brooks AS, Brouwer RW, Burns AJ, et al: Whole exome sequencing coupled with unbiased functional analysis reveals new Hirschsprung disease genes. Genome Biol. 18:482017. View Article : Google Scholar : PubMed/NCBI

100 

Halim D, Wilson MP, Oliver D, Brosens E, Verheij JB, Han Y, Nanda V, Lyu Q, Doukas M, Stoop H, et al: Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice. Proc Natl Acad Sci USA. 114:E2739–E2747. 2017. View Article : Google Scholar : PubMed/NCBI

101 

Dever DP, Bak RO, Reinisch A, Camarena J, Washington G, Nicolas CE, Pavel-Dinu M, Saxena N, Wilkens AB, Mantri S, et al: CRISPR/Cas9 β-globin gene targeting in human haematopoietic stem cells. Nature. 539:384–389. 2016. View Article : Google Scholar : PubMed/NCBI

102 

Ou Z, Niu X, He W, Chen Y, Song B, Xian Y, Fan D, Tang D and Sun X: The combination of CRISPR/Cas9 and iPSC technologies in the gene therapy of human β-thalassemia in mice. Sci Re. 6:324632016.

103 

Xie F, Ye L, Chang JC, Beyer AI, Wang J, Muench MO and Kan YW: Seamless gene correction of β-thalassemia mutations in patient-specific iPSCs using CRISPR/Cas9 and piggyBac. Genome Res. 24:1526–1533. 2014. View Article : Google Scholar : PubMed/NCBI

104 

Xu P, Tong Y, Liu XZ, Wang TT, Cheng L, Wang BY, Lv X, Huang Y and Liu DP: Both TALENs and CRISPR/Cas9 directly target the HBB IVS2 654 (C > T) mutation in β-thalassemia-derived iPSCs. Sci Rep. 5:120652015. View Article : Google Scholar

105 

Traxler EA, Yao Y, Wang YD, Woodard KJ, Kurita R, Nakamura Y, Hughes JR, Hardison RC, Blobel GA, Li C and Weiss MJ: A genome-editing strategy to treat β-hemoglobinopathies that recapitulates a mutation associated with a benign genetic condition. Nat Med. 22:987–990. 2016. View Article : Google Scholar : PubMed/NCBI

106 

Canver MC, Smith EC, Sher F, Pinello L, Sanjana NE, Shalem O, Chen DD, Schupp PG, Vinjamur DS, Garcia SP, et al: BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis. Nature. 527:192–197. 2015. View Article : Google Scholar : PubMed/NCBI

107 

Zhang N, Zhi H, Curtis BR, Rao S, Jobaliya C, Poncz M, French DL and Newman PJ: CRISPR/Cas9-mediated conversion of human platelet alloantigen allotypes. Blood. 127:675–680. 2016. View Article : Google Scholar :

108 

Osborn MJ, Gabriel R, Webber BR, DeFeo AP, McElroy AN, Jarjour J, Starker CG, Wagner JE, Joung JK, Voytas DF, et al: Fanconi anemia gene editing by the CRISPR/Cas9 system. Hum Gene Ther. 26:114–126. 2015. View Article : Google Scholar :

109 

Park CY, Kim DH, Son JS, Sung JJ, Lee J, Bae S, Kim JH, Kim DW and Kim JS: Functional correction of large factor VIII gene chromosomal inversions in hemophilia a patient-derived iPSCs using CRISPR-Cas9. Cell Stem Cell. 17:213–220. 2015. View Article : Google Scholar : PubMed/NCBI

110 

Zhang H and McCarty N: CRISPR-Cas9 technology and its application in haematological disorders. Br J Haematol. 175:208–225. 2016. View Article : Google Scholar : PubMed/NCBI

111 

Chen J, Jiang N, Wang T, Xie G, Zhang Z, Li H, Yuan J, Sun Z and Chen J: DNA shuffling of uricase gene leads to a more ‘human like’ chimeric uricase with increased uricolytic activity. Int J Biol Macromol. 82:522–529. 2016. View Article : Google Scholar

112 

Guan Y, Ma Y, Li Q, Sun Z, Ma L, Wu L, Wang L, Zeng L, Shao Y, Chen Y, et al: CRISPR/Cas9-mediated somatic correction of a novel coagulator factor IX gene mutation ameliorates hemophilia in mouse. EMBO Mol Med. 8:477–488. 2016. View Article : Google Scholar : PubMed/NCBI

113 

Hai T, Teng F, Guo R, Li W and Zhou Q: One-step generation of knockout pigs by zygote injection of CRISPR/Cas system. Cell Res. 24:372–375. 2014. View Article : Google Scholar : PubMed/NCBI

114 

Puschnik AS, Majzoub K, Ooi YS and Carette JE: A CRISPR toolbox to study virus-host interactions. Nat Rev Microbiol. 15:351–364. 2017. View Article : Google Scholar : PubMed/NCBI

115 

Kennedy EM, Kornepati AVR, Goldstein M, Bogerd HP, Poling BC, Whisnant AW, Kastan MB and Cullen BR: Inactivation of the human papillomavirus E6 or E7 gene in cervical carcinoma cells by using a bacterial CRISPR/Cas RNA-guided endonuclease. J Virol. 88:11965–11972. 2014. View Article : Google Scholar : PubMed/NCBI

116 

Wang W, Ye C, Liu J, Zhang D, Kimata JT and Zhou P: CCR5 gene disruption via lentiviral vectors expressing Cas9 and single guided RNA renders cells resistant to HIV-1 infection. PLoS One. 9:e1159872014. View Article : Google Scholar : PubMed/NCBI

117 

Zhen S, Hua L, Liu YH, Gao LC, Fu J, Wan DY, Dong LH, Song HF and Gao X: Harnessing the clustered regularly inter-spaced short palindromic repeat (CRISPR)/CRISPR-associated Cas9 system to disrupt the hepatitis B virus. Gene Ther. 22:404–412. 2015. View Article : Google Scholar : PubMed/NCBI

118 

Ramanan V, Shlomai A, Cox DBT, Schwartz RE, Michailidis E, Bhatta A, Scott DA, Zhang F, Rice CM and Bhatia SN: CRISPR/Cas9 cleavage of viral DNA efficiently suppresses hepatitis B virus. Sci Rep. 5:108332015. View Article : Google Scholar : PubMed/NCBI

119 

Karimova M, Beschorner N, Dammermann W, Chemnitz J, Indenbirken D, Bockmann JH, Grundhoff A, Lüth S, Buchholz F, Schulze zur Wiesch J and Hauber J: CRISPR/Cas9 nickase-mediated disruption of hepatitis B virus open reading frame S and X. Sci Rep. 5:137342015. View Article : Google Scholar : PubMed/NCBI

120 

Qi Xu Y, Luo Y, Yang J, Xie J, Deng Q, Su C, Wei N, Shi W, Xu DF, et al: Hepatitis B virus X protein stimulates proliferation, wound closure and inhibits apoptosis of HuH-7 cells via CDC42. Int J Mol Sci. 18:E5862017. View Article : Google Scholar

121 

Ren Q, Li C, Yuan P, Cai C, Zhang L, Luo GG and Wei W: A dual-reporter system for real-time monitoring and high-throughput CRISPR/Cas9 library screening of the hepatitis C virus. Sci Rep. 5:88652015. View Article : Google Scholar : PubMed/NCBI

122 

Yuen KS, Chan CP, Wong N-HM, Ho CH, Ho TH, Lei T, Deng W, Tsao SW, Chen H, Kok KH and Jin DY: CRISPR/Cas9-mediated genome editing of Epstein-Barr virus in human cells. J Gen Virol. 96:626–636. 2015. View Article : Google Scholar

123 

Wang J and Quake SR: RNA-guided endonuclease provides a therapeutic strategy to cure latent herpesviridae infection. Proc Natl Acad Sci USA. 111:13157–13162. 2014. View Article : Google Scholar : PubMed/NCBI

124 

Kistler KE, Vosshall LB and Matthews BJ: Genome engineering with CRISPR-Cas9 in the mosquito Aedes aegypti. Cell Rep. 11:51–60. 2015. View Article : Google Scholar : PubMed/NCBI

125 

Zhang C, Xiao B, Jiang Y, Zhao Y, Li Z, Gao H, Ling Y, Wei J, Li S, Lu M, et al: Efficient editing of malaria parasite genome using the CRISPR/Cas9 system. MBio. 5:e01414-142014. View Article : Google Scholar : PubMed/NCBI

126 

Wagner JC, Platt RJ, Goldfless SJ, Zhang F and Niles JC: Efficient CRISPR/Cas9-mediated genome editing in P. falciparum. Nat Methods. 11:915–918. 2014. View Article : Google Scholar : PubMed/NCBI

127 

Ghorbal M, Gorman M, Macpherson CR, Martins RM, Scherf A and Lopez-Rubio JJ: Genome editing in the human malaria parasite Plasmodium falciparum using the crisPr-cas9 system. Nat Biotechnol. 32:819–821. 2014. View Article : Google Scholar : PubMed/NCBI

128 

Burt A: Site-specific selfish genes as tools for the control and genetic engineering of natural populations. Proc Biol Sci. 270:921–928. 2003. View Article : Google Scholar : PubMed/NCBI

129 

Webber BL, Raghu S and Edwards OR: Opinion: Is CRISPR-based gene drive a biocontrol silver bullet or global conservation threat? Proc Natl Acad Sci USA. 112:10565–10567. 2015. View Article : Google Scholar : PubMed/NCBI

130 

Hammond A, Galizi R, Kyrou K, Simoni A, Siniscalchi C, Katsanos D, Gribble M, Baker D, Marois E, Russell S, et al: A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nat Biotechnol. 34:78–83. 2016. View Article : Google Scholar :

131 

Sánchez-Rivera FJ and Jacks T: Applications of the CRISPR-Cas9 system in cancer biology. Nat Rev Cancer. 15:387–395. 2015. View Article : Google Scholar : PubMed/NCBI

132 

Kawamura N, Nimura K, Nagano H, Yamaguchi S, Nonomura N and Kaneda Y: CRISPR/Cas9-mediated gene knockout of NANOG and NANOGP8 decreases the malignant potential of prostate cancer cells. Oncotarget. 6:22361–22374. 2015. View Article : Google Scholar : PubMed/NCBI

133 

García-Tuñón I, Hernández-Sánchez M, Ordoñez JL, Alonso-Pérez V, Álamo-Quijada M, Benito R, Guerrero C, Hernández-Rivas JM and Sánchez-Martín M: The CRISPR/Cas9 system efficiently reverts the tumorigenic ability of BCR/ABL in vitro and in a xenograft model of chronic myeloid leukemia. Oncotarget. 8:26027–26040. 2017. View Article : Google Scholar : PubMed/NCBI

134 

Zuckermann M, Hovestadt V, Knobbe-Thomsen CB, Zapatka M, Northcott PA, Schramm K, Belic J, Jones DT, Tschida B, Moriarity B, et al: Somatic CRISPR/Cas9-mediated tumour suppressor disruption enables versatile brain tumour modelling. Nat Commun. 6:73912015. View Article : Google Scholar : PubMed/NCBI

135 

Maddalo D, Manchado E, Concepcion CP, Bonetti C, Vidigal JA, Han YC, Ogrodowski P, Crippa A, Rekhtman N, de Stanchina E, et al: In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system. Nature. 516:423–427. 2014. View Article : Google Scholar : PubMed/NCBI

136 

Pathak S, McDermott MF and Savic S: Autoinflammatory diseases: Update on classification diagnosis and management. J Clin Pathol. 70:1–8. 2017. View Article : Google Scholar

137 

Sá DC: Inflammasomes and dermatology. An Bras Dermatol. 91:566–578. 2016. View Article : Google Scholar : PubMed/NCBI

138 

Kim K, Bang SY, Lee HS and Bae SC: Update on the genetic architecture of rheumatoid arthritis. Nat Rev Rheumatol. 13:13–24. 2017. View Article : Google Scholar

139 

Yang M, Zhang L, Stevens J and Gibson G: CRISPR/Cas9 mediated generation of stable chondrocyte cell lines with targeted gene knockouts; analysis of an aggrecan knockout cell line. Bone. 69:118–125. 2014. View Article : Google Scholar : PubMed/NCBI

140 

Tang S, Chen T, Yu Z, Zhu X, Yang M, Xie B, Li N, Cao X and Wang J: RasGRP3 limits toll-like receptor-triggered inflammatory response in macrophages by activating Rap1 small GTPase. Nat Commun. 5:46572014. View Article : Google Scholar : PubMed/NCBI

141 

Jing W, Zhang X, Sun W, Hou X, Yao Z and Zhu Y: CRISPR/CAS9-mediated genome editing of miRNA-155 inhibits proinflammatory cytokine production by RAW264.7 cells. Biomed Res Int. 2015.326042:2015.

142 

Ott de Bruin LM, Volpi S and Musunuru K: Novel genome-editing tools to model and correct primary immunodeficiencies. Front Immunol. 6:2502015. View Article : Google Scholar : PubMed/NCBI

143 

Cowan MJ, Neven B, Cavazanna-Calvo M, Fischer A and Puck J: Hematopoietic stem cell transplantation for severe combined immunodeficiency diseases. Biol Blood Marrow Transplant. 14(1 Suppl 1): S73–S75. 2008. View Article : Google Scholar

144 

Deakin CT, Alexander IE and Kerridge I: Accepting risk in clinical research: Is the gene therapy field becoming too risk-averse. Mol Ther. 17:1842–1848. 2009. View Article : Google Scholar : PubMed/NCBI

145 

Kohn DB and Kuo CY: New frontiers in the therapy of primary immunodeficiency: From gene addition to gene editing. J Allergy Clin Immunol. 139:726–732. 2017. View Article : Google Scholar : PubMed/NCBI

146 

Goodman MA, Moradi Manesh D, Malik P and Rothenberg ME: CRISPR/Cas9 in allergic and immunologic diseases. Expert Rev Clin Immunol. 13:5–9. 2017. View Article : Google Scholar

147 

Wang M, Glass ZA and Xu Q: Non-viral delivery of genome-editing nucleases for gene therapy. Gene Ther. 24:144–150. 2017. View Article : Google Scholar

148 

Chang CW, Lai YS, Westin E, Khodadadi-Jamayran A, Pawlik KM, Lamb LS Jr, Goldman FD and Townes TM: Modeling human severe combined immunodeficiency and correction by CRISPR/Cas9-enhanced gene targeting. Cell Rep. 12:1668–1677. 2015. View Article : Google Scholar : PubMed/NCBI

149 

Flynn R, Grundmann A, Renz P, Hänseler W, James WS, Cowley SA and Moore MD: CRISPR-mediated genotypic and phenotypic correction of a chronic granulomatous disease mutation in human iPS cells. Exp Hematol. 43:838–848. e32015. View Article : Google Scholar : PubMed/NCBI

150 

Wrona D, Siler U and Reichenbach J: CRISPR/Cas9-generated p47(phox)-deficient cell line for chronic granulomatous disease gene therapy vector development. Sci Rep. 7:441872017. View Article : Google Scholar

151 

Yan Q, Zhang Q, Yang H, Zou Q, Tang C, Fan N and Lai L: Generation of multi-gene knockout rabbits using the Cas9/gRNA system. Cell Regen (Lond). 3:122014.

152 

Fan Z, Li W, Lee SR, Meng Q, Shi B, Bunch TD, White KL, Kong IK and Wang Z: Efficient gene targeting in golden Syrian hamsters by the CRISPR/Cas9 system. PLoS One. 9:e1097552014. View Article : Google Scholar : PubMed/NCBI

153 

Chen F, Wang Y, Yuan Y, Zhang W, Ren Z, Jin Y, Liu X, Xiong Q, Chen Q, Zhang M, et al: Generation of B cell-deficient pigs by highly efficient CRISPR/Cas9-mediated gene targeting. J Genet Genomics. 42:437–444. 2015. View Article : Google Scholar : PubMed/NCBI

154 

Chu HW, Rios C, Huang C, Wesolowska-Andersen A, Burchard EG, O’Connor BP, Fingerlin TE, Nichols D, Reynolds SD and Seibold MA: CRISPR-Cas9-mediated gene knockout in primary human airway epithelial cells reveals a proinflammatory role for MUC18. Gene Ther. 22:822–829. 2015. View Article : Google Scholar : PubMed/NCBI

155 

Kuo CY, Hoban MD, Joglekar AV and Kohn DB: Site specific gene correction of defects in CD40 ligand using the Crispr/Cas9 genome editing platform. J Allergy Clin Immunol. 135:AB172015. View Article : Google Scholar

156 

Cheong TC, Compagno M and Chiarle R: Editing of mouse and human immunoglobulin genes by CRISPR-Cas9 system. Nat Commun. 7:109342016. View Article : Google Scholar : PubMed/NCBI

157 

Rodriguez-Sanchez IP, Guindon J, Ruiz M, Tejero ME, Hubbard G, Martinez-de-Villarreal LE, Barrera-Saldaña HA, Dick EJ Jr, Comuzzie AG and Schlabritz-Loutsevitch NE: The endocannabinoid system in the baboon (Papio spp.) as a complex framework for developmental pharmacology. Neurotoxicol Teratol. 58:23–30. 2016. View Article : Google Scholar : PubMed/NCBI

158 

Niu Y, Shen B, Cui Y, Chen Y, Wang J, Wang L, Kang Y, Zhao X, Si W, Li W, et al: Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos. Cell. 156:836–843. 2014. View Article : Google Scholar : PubMed/NCBI

159 

Kang Y, Zheng B, Shen B, Chen Y, Wang L, Wang J, Niu Y, Cui Y, Zhou J, Wang H, et al: CRISPR/Cas9-mediated Dax1 knockout in the monkey recapitulates human AHC-HH. Hum Mol Genet. 24:7255–7264. 2015. View Article : Google Scholar : PubMed/NCBI

160 

Kim S, Huang LW, Snow KJ, Ablamunits V, Hasham MG, Young TH, Paulk AC, Richardson JE, Affourtit JP, Shalom-Barak T, et al: A mouse model of conditional lipodystrophy. Proc Natl Acad Sci USA. 104:16627–16632. 2007. View Article : Google Scholar : PubMed/NCBI

161 

Croasdell A, Duffney PF, Kim N, Lacy SH, Sime PJ and Phipps RP: PPARγ and the innate immune system mediate the resolution of inflammation. PPAR Res. 2015.549691:2015.

162 

Huang J, Guo X, Fan N, Song J, Zhao B, Ouyang Z, Liu Z, Zhao Y, Yan Q, Yi X, et al: RAG1/2 knockout pigs with severe combined immunodeficiency. J Immunol. 193:1496–1503. 2014. View Article : Google Scholar : PubMed/NCBI

163 

Chen Y, Xiong M, Dong Y, Haberman A, Cao J, Liu H, Zhou W and Zhang SC: Chemical control of grafted human PSC-derived neurons in a mouse model of Parkinson’s disease. Cell Stem Cell. 18:817–826. 2016. View Article : Google Scholar : PubMed/NCBI

164 

Zhou X, Xin J, Fan N, Zou Q, Huang J, Ouyang Z, Zhao Y, Zhao B, Liu Z, Lai S, et al: Generation of CRISPR/Cas9-mediated gene-targeted pigs via somatic cell nuclear transfer. Cell Mol Life Sci. 72:1175–1184. 2015. View Article : Google Scholar

165 

Wang L, Yi F, Fu L, Yang J, Wang S, Wang Z, Suzuki K, Sun L, Xu X, Yu Y, et al: CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs. Protein Cell. 8:365–378. 2017. View Article : Google Scholar : PubMed/NCBI

166 

Bhinge A, Namboori SC, Zhang X, VanDongen AMJ and Stanton LW: Genetic correction of SOD1 mutant iPSCs reveals ERK and JNK activated AP1 as a driver of neurodegeneration in amyotrophic lateral sclerosis. Stem Cell Reports. 8:856–869. 2017. View Article : Google Scholar : PubMed/NCBI

167 

Merienne N, Vachey G, de Longprez L, Meunier C, Zimmer V, Perriard G, Canales M, Mathias A, Herrgott L, Beltraminelli T, et al: The self-inactivating KamiCas9 system for the editing of CNS disease genes. Cell Rep. 20:2980–2991. 2017. View Article : Google Scholar : PubMed/NCBI

168 

Page SC, Hamersky GR, Gallo RA, Rannals MD, Calcaterra NE, Campbell MN, Mayfield B, Briley A, Phan BN, Jaffe AE and Maher BJ: The schizophrenia- and autism-associated gene, transcription factor 4 regulates the columnar distribution of layer 2/3 prefrontal pyramidal neurons in an activity-dependent manner. Mol Psychiatry. 23:304–315. 2018. View Article : Google Scholar

169 

Long C, Amoasii L, Mireault AA, McAnally JR, Li H, Sanchez-Ortiz E, Bhattacharyya S, Shelton JM, Bassel-Duby R and Olson EN: Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science. 351:400–403. 2016. View Article : Google Scholar : PubMed/NCBI

170 

Long C, McAnally JR, Shelton JM, Mireault AA, Bassel-Duby R and Olson EN: Prevention of muscular dystrophy in mice by CRISPR/Cas9-mediated editing of germline DNA. Science. 345:1184–1188. 2014. View Article : Google Scholar : PubMed/NCBI

171 

Nelson CE, Hakim CH, Ousterout DG, Thakore PI, Moreb EA, Castellanos Rivera RM, Madhavan S, Pan X, Ran FA, Yan WX, et al: In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science. 351:403–407. 2016. View Article : Google Scholar : PubMed/NCBI

172 

Tabebordbar M, Zhu K, Cheng JKW, Chew WL, Widrick JJ, Yan WX, Maesner C, Wu EY, Xiao R, Ran FA, et al: In vivo gene editing in dystrophic mouse muscle and muscle stem cells. Science. 351:407–411. 2016. View Article : Google Scholar : PubMed/NCBI

173 

Ackermann AM, Zhang J, Heller A, Briker A and Kaestner KH: High-fidelity Glucagon-CreER mouse line generated by CRISPR-Cas9 assisted gene targeting. Mol Metab. 6:236–244. 2017. View Article : Google Scholar : PubMed/NCBI

174 

Jarrett KE, Lee CM, Yeh YH, Hsu RH, Gupta R, Zhang M, Rodriguez PJ, Lee CS, Gillard BK, Bissig KD, et al: Somatic genome editing with CRISPR/Cas9 generates and corrects a metabolic disease. Sci Rep. 7:446242017. View Article : Google Scholar : PubMed/NCBI

175 

Mookherjee Yu W, Chaitankar S, Hiriyanna V, Kim S, Brooks JW, Ataeijannati M, Sun Y, Dong X, Li LT, et al: Nrl knockdown by AAV-delivered CRISPR/Cas9 prevents retinal degeneration in mice. Nat Commun. 8:147162017. View Article : Google Scholar : PubMed/NCBI

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April 2019
Volume 43 Issue 4

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APA
Rodríguez‑Rodríguez, D.R., Ramírez‑Solís, R., Garza‑Elizondo, M.A., Garza‑Rodríguez, M.D., & Barrera‑Saldaña, H.A. (2019). Genome editing: A perspective on the application of CRISPR/Cas9 to study human diseases (Review). International Journal of Molecular Medicine, 43, 1559-1574. https://doi.org/10.3892/ijmm.2019.4112
MLA
Rodríguez‑Rodríguez, D. R., Ramírez‑Solís, R., Garza‑Elizondo, M. A., Garza‑Rodríguez, M. D., Barrera‑Saldaña, H. A."Genome editing: A perspective on the application of CRISPR/Cas9 to study human diseases (Review)". International Journal of Molecular Medicine 43.4 (2019): 1559-1574.
Chicago
Rodríguez‑Rodríguez, D. R., Ramírez‑Solís, R., Garza‑Elizondo, M. A., Garza‑Rodríguez, M. D., Barrera‑Saldaña, H. A."Genome editing: A perspective on the application of CRISPR/Cas9 to study human diseases (Review)". International Journal of Molecular Medicine 43, no. 4 (2019): 1559-1574. https://doi.org/10.3892/ijmm.2019.4112