Review Article


DOI :10.26650/EurJBiol.2019.0024   IUP :10.26650/EurJBiol.2019.0024    Full Text (PDF)

CRISPR-Cas: Removing Boundaries of the Nature

Nicat CebrailoğluAli Burak YıldızÖzlem AkkayaYelda Özden Çiftçi

The CRISPR-Cas 9 system, which is known as a natural way of bacteria to defend against phage infection and plasmid transfer, has been re-purposed as a RNA-guided DNA targeting strategy for genome editing. Together with the advances gained in DNA sequencing technology, this platform opened a new era in molecular biology since its recognition was specified by 20-nt single-guide RNA which made technique easier, efficient and simple for application in any organism. Thus, many studies have discussed and performed the applications of CRISPR-Cas systems on different organisms for genome editing. Moreover, targeted gene regulations, epigenetic modulation, chromatin imaging and manipulation could also be applied with this system. Besides all its potential promising aspects, this tool might have some side effects like off-target mutations. In addition, unexpected results have also been reported after some gene editing applications. Thus, this review provides a brief history of gene editing tools together with the overview of the latest applications, regulations and ethical/structural aspects of the CRISPR Cas system.

PDF View

References

  • 1. Adli M. The CRISPR tool kit for genome editing and beyond. Nat Commun 2018; 9(1): 1911. google scholar
  • 2. Capecchi MR. Altering the genome by homologous recombination. Sci 1989; 244(4910): 1288-92. 3. Lin FL, Sperle K, Sternberg N. Recombination in mouse L cells between DNA introduced into cells and homologous chromosomal sequences. Proc Natl Acad Sci USA 1985; 82: 1391–95. google scholar
  • 4. Klug A, Rhodes D. ‘Zinc fingers’: a novel protein motif for nucleic acid recognition. Trends Biochem Sci 1987; 12: 464-69. google scholar
  • 5. Kim YG, Cha J, Chandrasegaran S. Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. PNAS 1996; 93(3): 1156-60. google scholar
  • 6. Urnov FD, Miller JC, Lee YL, Beausejour CM, Rock JM, Augustus S, et al. Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 2005; 435(7042): 646. google scholar
  • 7. Christian M, Cermak T, Doyle EL, Schmidt C, Zhang F, Hummel A, Targeting DNA double-strand breaks with TAL effector nucleases. Genetics 2010; 186(2): 757-761. google scholar
  • 8. Doudna JA, Charpentier E, The new frontier of genome engineering with CRISPR-Cas9. Sci 2014; 346(6213): 1258096. google scholar
  • 9. Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell 2014; 157(6), 1262-78. google scholar
  • 10. Leenay RT, Maksimchuk KR, Slotkowski RA, Agrawal RN, Gomaa AA, Briner AE, Barrangou R, Beisel CL. Identifying and visualizing functional PAM diversity across CRISPR-Cas systems. Mol Cell 2016, 62(1): 137-47. google scholar
  • 11. Liu JJ, Orlova N, Oakes BL, Ma E, Spinner HB, Baney KL, Al-Shayeb B. CasX enzymes comprise a distinct family of RNA-guided genome editors. Nature 2019; 566(7743): 218. google scholar
  • 12. Harrington LB, Burstein D, Chen JS, Paez-Espino D, Ma E, Witte IP, Doudna JA. Programmed DNA destruction by miniature CRISPRCas14 enzymes. Sci 2018; 362(6416): 839-42. google scholar
  • 13. Li SY, Cheng QX, Liu JK, Nie XQ, Zhao GP, Wang J. CRISPR-Cas12a has both cis-and trans-cleavage activities on single-stranded DNA. Cell Res 2018; 28(4): 491. google scholar
  • 14. Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR. Programmable editing of a target base in genomic DNA without doublestranded DNA cleavage. Nature 2016; 533:420–24. google scholar
  • 15. Gaudelli NM, Komor AC, Rees HA, Packer MS, Badran AH, Bryson DI, Liu DR. Programmable base editing of A*T to G*C in genomic DNA without DNA cleavage. Nature 2017; 551:464–71. google scholar
  • 16. Maeder ML, Linder SJ, Cascio VM, Fu Y, Ho QH, Joung JK. CRISPR RNA–guided activation of endogenous human genes. Nat Methods 2013; 10(10): 977. google scholar
  • 17. Gilbert LA, Larson MH, Morsut L, Liu Z, Brar GA, Torres SE, Lim WA. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 2013; 154(2): 442-51. google scholar
  • 18. McDonald JI, Celik H, Rois LE, Fishberger G, Fowler T, Rees R,Challen GA. Reprogrammable CRISPR/Cas9-based system for inducing site-specific DNA methylation. Biol Open 2016; 5(6): 866-74. google scholar
  • 19. Cox DB, Gootenberg JS, Abudayyeh OO, Franklin B, Kellner MJ, Joung J, Zhang F. RNA editing with CRISPR-Cas13. Sci 358(6366), 2017; 1019-27. google scholar
  • 20. Chen S, Lee B, Lee AYF, Modzelewski AJ, He L. Highly efficient mouse genome editing by CRISPR ribonucleoprotein electroporation of zygotes. J Biol Chem 2016; 291(28): 14457-67. google scholar
  • 21. Fakhiri J, Nickl M,Grimm D. Rapid and Simple Screening of CRISPR Guide RNAs (gRNAs) in Cultured Cells Using Adeno-Associated Viral (AAV) Vectors. In CRISPR Gene Editing, 2019; (pp. 111-126). Humana Press, New York, NY. google scholar
  • 22. Malcolm T, Khalili K. U.S. Patent Application, 2018; No. 15/873,483. google scholar
  • 23. Ali Z, Abul-Faraj A, Li L, Ghosh N, Piatek M, Mahjoub A, DineshKumar S. Efficient virus-mediated genome editing in plants using the CRISPR/Cas9 system. Mol Plant 2015; 8(8): 1288-91. google scholar
  • 24. Li L, Hu S, Chen X. Non-viral delivery systems for CRISPR/Cas9-based genome editing: Challenges and opportunities. Biomaterials 2018; 171: 207-18. google scholar
  • 25. Veillet F, Perrot L, Chauvin L, Kermarrec MP, Guyon-Debast A, Chauvin JE, Mazier M. Transgene-Free Genome Editing in Tomato and Potato Plants Using Agrobacterium-Mediated Delivery of a CRISPR/Cas9 Cytidine Base Editor. Int J Mo. Sci 2019; 20(2): 402. google scholar
  • 26. Nekrasov V, Wang C, Win J, Lanz C, Weigel D, Kamoun S. Rapid generation of a transgene-free powdery mildew resistant tomato by genome deletion. Sci Rep 2017; 7(1): 482. google scholar
  • 27. Woo JW, Kim J, Kwon SI, Corvalán C, Cho SW, Kim H, Kim JS. DNAfree genome editing in plants with preassembled CRISPR-Cas9 ribonucleoproteins. Nat Biotechnol 2015; 33(11): 1162. google scholar
  • 28. Liang Z, Zhang K, Chen K, Gao C. Targeted mutagenesis in Zea mays using TALENs and the CRISPR/Cas system. J Genet Genomics 2014; 41(2): 63-68. google scholar
  • 29. Bondy-Denomy J, Garcia B, Strum S, Du M, Rollins MF, HidalgoReyes Y, Davidson AR, Multiple mechanisms for CRISPR–Cas inhibition by anti-CRISPR proteins. Nature 2015; 526(7571): 136. google scholar
  • 30. Wu Y, Liang D, Wang Y, Bai M, Tang W, Bao S, Yan Z, Li D, Li J. Correction of a Genetic Disease in Mouse via Use of CRISPRCas9. Cell Stem Cell 2013;13:659–62. google scholar
  • 31. Long C, McAnally JR, Shelton JM, Mireault AA, Bassel-Duby R, Olson EN. Prevention of muscular dystrophy in mice by CRISPRCas9–mediated editing of germline DNA. Sci 2014;345:1184–88. google scholar
  • 32. Maji B, Gangopadhyay SA, Lee M, Shi M, Wu P, Heler R, Mok B, Lim D, Siriwardena SU, Paul B, Dančík V. A high-throughput platform to identify small-molecule inhibitors of CRISPR-Cas9. Cell 2019;177(4): 1067-79. google scholar
  • 33. Liu JJ, Orlova N, Oakes BL, Ma E, Spinner HB, Baney KL, Chuck J, Tan D, Knott GJ, Harrington LB, Al-Shayeb B. CasX enzymes comprise a distinct family of RNA-guided genome editors. Nature 2019; 566(7743): 218. google scholar
  • 34. Technology Review, 2019, http://www.technologyreview.com. Last accessed June 3, 2019. google scholar
  • 35. Thakore PI, Black JB, Hilton IB, Gersbach CA. Editing the epigenome: technologies for programmable transcription and epigenetic modulation. Nat Methods 2016; 13: 127–37. google scholar
  • 36. Klann TS. CRISPR-Cas9 epigenome editing enables highthroughput screening for functional regulatory elements in the human genome. Nat Biotechnol 2017; 35: 561–68. google scholar
  • 37. Simeonov DR. Discovery of stimulation-responsive immune enhancers with CRISPR activation. Nature 2017: 549:111-5. google scholar
  • 38. Liu SJ, CRISPRi-based genome-scale identification of functional long noncoding RNA loci in human cells. Sci 2017; aah7111. google scholar
  • 39. Fujita T, Fujii H. Efficient isolation of specific genomic regions and identification of associated proteins by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) using CRISPR. Biochem Biophys Res Commun 2013; 439: 132–36. google scholar
  • 40. Fujita T, Fuji H. Identification of proteins associated with an IFNγresponsive promoter by a retroviral expression system for enChIP using CRISPR. PLOS ONE 9 2014; e103084. google scholar
  • 41. Sanjana NE. Genome-scale CRISPR pooled screens. Anal Biochem 2017; 532: 95-99. google scholar
  • 42. Shalem O, Sanjana NE, Zhang F. High-throughput functional genomics using CRISPR-Cas9. Nat Rev Genet 2015;16: 299–311. google scholar
  • 43. Shi J, Wang E, Milazzo JP, Wang Z, Kinney JB, Vakoc CR. Discovery of cancer drug targets by CRISPR-Cas9 screening of protein domains. Nat Biotech 2015;33: 661–67. google scholar
  • 44. Chen Y, Zhang Y. Application of the CRISPR/Cas9 system to drug resistance in breast cancer. Adv Sci 2018; 5:1700964. google scholar
  • 45. Parnas O, Jovanovic M, Eisenhaure Thomas M, Herbst Rebecca H, Dixit A, Ye Chun J, Przybylski D, Platt Randall J, Tirosh I, Sanjana Neville E, et al. A genome-wide crıspr screen in primary immune cells to dissect regulatory networks. Cell 2015;162:675–86. google scholar
  • 46. Zhou Y, Zhu S, Cai C, Yuan P, Li C, Huang Y, Wei W. High-throughput screening of a CRISPR-Cas9 library for functional genomics in human cells. Nature 2014;509:487–91. google scholar
  • 47. Kiani S, Chavez A, Tuttle M, Hall RN, Chari R, Ter-Ovanesyan D, Qian J, Pruitt BW, Beal J, Vora S, et al. Cas9 gRNA engineering for genome editing, activation and repression. Nat Methods 2015;12:1051–54. google scholar
  • 48. Sun Y, Jiao G, Liu Z, Zhang X, Li J, Guo X, Xia L. Generation of highamylose rice through CRISPR/Cas9-mediated targeted mutagenesis of starch branching enzymes. Front Plant Sci 2017; 8: 298. google scholar
  • 49. Rodríguez-Leal D, Lemmon ZH, Man J, Bartlett ME, Lippman ZB. Engineering quantitative trait variation for crop improvement by genome editing. Cell 2017; 171(2): 470-80. google scholar
  • 50. Soyk S, Müller NA, Park SJ, Schmalenbach I, Jiang K, Hayama R, Lippman ZB. Variation in the flowering gene SELF PRUNING 5G promotes dayneutrality and early yield in tomato. Nat Genet 2017; 49(1): 162. google scholar
  • 51. Hu B, Li D, Liu X, Qi J, Gao D, Zhao S, Yang L. Engineering non-transgenic gynoecious cucumber using an improved transformation protocol and optimized CRISPR/Cas9 system. Mol Plant 2017; 10(12): 1575-78. google scholar
  • 52. Okuzaki A, Ogawa T, Koizuka C, Kaneko K, Inaba M, Imamura J, Koizuka N. CRISPR/Cas9-mediated genome editing of the fatty acid desaturase 2 gene in Brassica napus. Plant Physiol Biochem 2018; 131: 63-69. google scholar
  • 53. Li J, Meng X, Zong Y, Chen K, Zhang H, Liu J, Gao C. Gene replacements and insertions in rice by intron targeting using CRISPR–Cas9. Nat Plants 2016; 2(10): 16139. google scholar
  • 54. Shimatani Z, Ariizumi T, Fujikura U, Kondo A, Ezura H, Nishida K. Targeted base editing with crispr-deaminase in tomato. ın plant genome editing with crispr systems. Humana Press, New York 2019; 297-307. google scholar
  • 55. Peng A, Chen S, Lei T, Xu L, He Y, Wu L, Yao L, Zou X. Engineering canker‐resistant plants through CRISPR/Cas9‐targeted editing of the susceptibility gene Cs LOB 1 promoter in citrus. Plant Biotechnol J 2017; 15(12): 1509-19. google scholar
  • 56. Zhang A, Liu Y, Wang F, Li T, Chen Z, Kong D, Bi J, Zhang F, Luo X, Wang J, Tang J, Yu X, Liu G, Luo L. Enhanced rice salinity tolerance via CRISPR/Cas9-targeted mutagenesis of the OsRR22 gene. Mol Breeding 2019; 39(3): 47. google scholar
  • 57. Paixão JFR, Gillet FX, Ribeiro TP, Bournaud C, Lourenço-Tessutti IT, Noriega DD, Grossi-de-Sa MF. Improved drought stress tolerance in Arabidopsis by CRISPR/dCas9 fusion with a Histone AcetylTransferase. Sci Rep 2019; 9(1): 8080. google scholar
  • 58. McGill M. Plant Genome Editing Using CRISPR/Cas9: Investigating the role of ten1 in the maintenance and protection of telomeres in Arabidopsis thaliana 2019; Celebrating Scholarship and Creativity Day. google scholar
  • 59. Zhao P, You Q, Lei MA. CRISPR/Cas9 deletion into the phosphate transporter SlPHO1; 1 reveals its role in phosphate nutrition of tomato seedlings. Physiol Plant 2018. google scholar
  • 60. Veillet F, Perrot L, Chauvin L, Kermarrec MP, Guyon-Debast A, Chauvin JE, Mazier M. Transgene-free genome editing in tomato and potato plants using agrobacterium-mediated delivery of a CRISPR/Cas9 cytidine base editor. Int J Mol Sci 2019; 20(2): 402. google scholar
  • 61. Zsögön A, Čermák T, Naves ER, Notini MM, Edel KH, Weinl S, Peres LEP. De novo domestication of wild tomato using genome editing. Nature Biotechnol 2018; 36: 1211–16. 62. Calyxt, First commercial sale of calyxt high oleic soybean oil on the U.S. market, Press Release, 2019. google scholar
  • 63. Jiang Y, Chen B, Duan C, Sun B, Yang J, Yang S. Multigene editing in the Escherichia coli genome via the CRISPR-Cas9 system. Appl Environ Microbiol 2015; 81(7): 2506-14. google scholar
  • 64. Wang Y, Zhang ZT, Seo SO, Lynn P, Lu T, Jin YS, Blaschek HP. Gene transcription repression in Clostridium beijerinckii using CRISPRdCas9. Biotechnol Bioeng 2016 113(12): 2739-43. google scholar
  • 65. Zhu DK, Yang XQ, He Y, Zhou WS, Song XH, Wang JB, Zhang Y, Liu MF, Wang MS, Jia RY, Chen S, Sun KF, Yang Q, Wu Y, Chen XY, Cheng AC. Comparative genomic analysis identifies structural features of CRISPR-Cas systems in Riemerella anatipestifer. BMC genomics 2016; 17(1): 689. google scholar
  • 66. Song X, Huang H, Xiong Z, Ai L, Yang S. CRISPR-Cas9D10A nickaseassisted genome editing in Lactobacillus casei. Appl Environ Microbiol 2017 83(22): e01259-17. 67. Aparicio T, de Lorenzo V, Martínez‐García E. CRISPR/Cas9based counter selection boosts recombineering efficiency in Pseudomonas putida. Biotechnol J 2018; 13(5): 1700161. google scholar
  • 68. Medina-Aparicio L, Dávila S, Rebollar-Flores JE, Calva E, HernándezLucas I. The CRISPR-Cas system in Enterobacteriaceae. Pathogens and disease 2018; 76(1): fty002. google scholar
  • 69. Li K, Cai D, Wang Z, He Z, Chen S. Development of an efficient genome editing tool in Bacillus licheniformis using CRISPR-Cas9 nickase. Appl Environ Microbiol 2018; 84(6): e02608-17. google scholar
  • 70. Xiao Y, Wang S, Rommelfanger S, Balassy A, Barba‐Ostria C, Gu P, Galazka JM, Zhang F. Developing a Cas9‐based tool to engineer native plasmids in Synechocystis sp. PCC 6803. Biotechnol Bioeng 2018; 115(9): 2305-14. google scholar
  • 71. Li L, Wei K, Zheng G, Liu X, Chen S, Jiang W, Lu Y. CRISPR-Cpf1assisted multiplex genome editing and transcriptional repression in Streptomyces. Appl Environ Microbiol 2018 84(18): e00827-18. google scholar
  • 72. Wang Y, Liu Y, Liu J, Guo Y, Fan L, Ni X, Zhang X, Wang M, Zheng P, Sun J, Ma Y. MACBETH: multiplex automated Corynebacterium glutamicum base editing method. Metab Eng 2018; 47:200-10. google scholar
  • 73. Shariat N. The combination of CRISPR–MVLST and PFGE provides increased discriminatory power for differentiating human clinical isolates of Salmonella enterica subsp. enterica serovar Enteritidis. Food Microbiol 2013; 34: 164–73. google scholar
  • 74. Barrangou R. Genomic impact of CRISPR immunization against bacteriophages. Biochem Soc Trans 2013; 41: 1383–91. google scholar
  • 75. Barrangou R, Horvath P. CRISPR: new horizons in phage resistance and strain identification. Annu Rev Food Sci Technol 2013; 3: 143–62. google scholar
  • 76. Gomaa AA. Programmable removal of bacterial strains by use of genome-targeting CRISPR–Cas systems. MBio 2014; 5: e00928– e1013. 77. Bondy-Denomy J, and Davidson AR. To acquire or resist: the complex biological effects of CRISPR–Cas systems. Trends Microbiol 2014; 22: 218–25. google scholar
  • 78. Martin-Laffon J, Kuntz M, Ricroch AE, inventors. Worldwide CRISPR patent landscape shows strong geographical biases. Nat Biotechnol 2019; 37(6):613-20. google scholar
  • 79. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA–guided DNA endonuclease in adaptive bacterial immunity. Sci 2012; 337(6096): 816-21. google scholar
  • 80. Swiech L, Heidenreich M, Banerjee A, Habib N, Li Y, Trombetta J, Zhang, F. In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9. Nature Biotechnol 2015; 33(1): 102. google scholar
  • 81. Jacobi AM, Rettig GR, Turk R, Collingwood MA, Zeiner SA, Quadros RM, Gurumurthy CB. Simplified CRISPR tools for efficient genome editing and streamlined protocols for their delivery into mammalian cells and mouse zygotes. Methods 2017; 121: 16-28. google scholar
  • 82. Amoasii L, Hildyard JC, Li H, Sanchez-Ortiz E, Mireault A, Caballero D, Bassel-Duby R. Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy. Sci 2018; 362(6410): 86-91. google scholar
  • 83. Santiago-Fernández O, Osorio FG, Quesada V, Rodríguez F, Basso S, Maeso D, Freije JM. Development of a CRISPR/Cas9-based therapy for Hutchinson–Gilford progeria syndrome. Nat Med 2019; 1. google scholar
  • 84. Ihry RJ, Worringer KA, Salick MR, Frias E, Ho D, Theriault K, Randhawa R. p53 inhibits CRISPR–Cas9 engineering in human pluripotent stem cells. Nat Med 2018; 24(7): 939. google scholar
  • 85. Schaefer KA, Wu WH, Colgan DF, Tsang SH, Bassuk AG, Mahajan VB. Unexpected mutations after CRISPR–Cas9 editing in vivo. Nat Met 2017;14(6): 547. google scholar
  • 86. Beaumont KA, Shekar SN, Cook AL, Duffy DL, Sturm RA. Red hair is the null phenotype of MC1R. Hum Mutat 2008; 29(8): E88-E94. google scholar
  • 87. Deng S, Kongpan LI, Wang F, Ning LI, Liu G, Zhao Y, Lian Z. One-step generation of myostatin gene knockout sheep via the CRISPR/ Cas9 system 2014; 1: 2-5. google scholar
  • 88. Lu Y, Xue J, Deng T, Zhou X, Yu K, Huang M, Gong Y. A phase I trial of PD-1 deficient engineered T cells with CRISPR/Cas9 in patients with advanced non-small cell lung cancer. 2018. google scholar
  • 89. June CH, O’Connor RS, Kawalekar OU, Ghassemi S, Milone MC. CAR T cell immunotherapy for human cancer. Sci 2018; 359(6382): 1361-65. google scholar
  • 90. Normile D. Shock greets claim of CRISPR-edited babies 2018. google scholar
  • 91. Wei X, Nielsen R. CCR5-∆ 32 is deleterious in the homozygous state in humans. Nat Med 2019; 1. google scholar
  • 92. OGTR, Office of the Gene Technology Regulator, Questions & answers on the technical review of the gene technology regulations 2001 (10 April 2019). google scholar
  • 93. World Trade Organization (WTO) Committee on Sanitary and Phytosanitary Measures, International Statement on Agricultural Applications of Precision Biotechnology (Oct. 30, 2018). google scholar
  • 94. Eriksson D, Kershen D, Nepomuceno A, Pogson BJ, Prieto H, Purnhagen K, Whelan A. A comparison of the EU regulatory approach to directed mutagenesis with that of other jurisdictions, consequences for international trade and potential steps forward. New Phytol 2019; 222(4): 1673-84. google scholar
  • 95. Dobrovidova O. Russia joins in global gene-editing bonanza. Nature 2018; 569(7756): 319. google scholar
  • 96. NHK World–Japan. 2018.Govt. Panel to not regulate some genome editing. [WWW document] URL https://www3.nhk.or.jp/nhkworld/ en/news/20180821_14/ [accessed 21 August 2018]. google scholar
  • 97. Callaway E. CRISPR plants now subject to tough GM laws in European Union 2018; Nature 560(7716):16. google scholar
  • 98. Kupferschmidt K. EU verdict on CRISPR crops dismays scientists 2018. google scholar
  • 99. Euractive. The EU future of new plant breeding techniques, Special Report May 2019 http://eurac.tv/9qiu google scholar
  • 100. Jeggo PA. Identification of genes involved in repair of DNA doublestrand breaks in mammalian cells. Radiat Res 1998; 150(5s): S80-S91. google scholar

Citations

Copy and paste a formatted citation or use one of the options to export in your chosen format


EXPORT



APA

Cebrailoğlu, N., Yıldız, A.B., Akkaya, Ö., & Özden Çiftçi, Y. (2019). CRISPR-Cas: Removing Boundaries of the Nature. European Journal of Biology, 78(2), 157-164. https://doi.org/10.26650/EurJBiol.2019.0024


AMA

Cebrailoğlu N, Yıldız A B, Akkaya Ö, Özden Çiftçi Y. CRISPR-Cas: Removing Boundaries of the Nature. European Journal of Biology. 2019;78(2):157-164. https://doi.org/10.26650/EurJBiol.2019.0024


ABNT

Cebrailoğlu, N.; Yıldız, A.B.; Akkaya, Ö.; Özden Çiftçi, Y. CRISPR-Cas: Removing Boundaries of the Nature. European Journal of Biology, [Publisher Location], v. 78, n. 2, p. 157-164, 2019.


Chicago: Author-Date Style

Cebrailoğlu, Nicat, and Ali Burak Yıldız and Özlem Akkaya and Yelda Özden Çiftçi. 2019. “CRISPR-Cas: Removing Boundaries of the Nature.” European Journal of Biology 78, no. 2: 157-164. https://doi.org/10.26650/EurJBiol.2019.0024


Chicago: Humanities Style

Cebrailoğlu, Nicat, and Ali Burak Yıldız and Özlem Akkaya and Yelda Özden Çiftçi. CRISPR-Cas: Removing Boundaries of the Nature.” European Journal of Biology 78, no. 2 (Apr. 2024): 157-164. https://doi.org/10.26650/EurJBiol.2019.0024


Harvard: Australian Style

Cebrailoğlu, N & Yıldız, AB & Akkaya, Ö & Özden Çiftçi, Y 2019, 'CRISPR-Cas: Removing Boundaries of the Nature', European Journal of Biology, vol. 78, no. 2, pp. 157-164, viewed 27 Apr. 2024, https://doi.org/10.26650/EurJBiol.2019.0024


Harvard: Author-Date Style

Cebrailoğlu, N. and Yıldız, A.B. and Akkaya, Ö. and Özden Çiftçi, Y. (2019) ‘CRISPR-Cas: Removing Boundaries of the Nature’, European Journal of Biology, 78(2), pp. 157-164. https://doi.org/10.26650/EurJBiol.2019.0024 (27 Apr. 2024).


MLA

Cebrailoğlu, Nicat, and Ali Burak Yıldız and Özlem Akkaya and Yelda Özden Çiftçi. CRISPR-Cas: Removing Boundaries of the Nature.” European Journal of Biology, vol. 78, no. 2, 2019, pp. 157-164. [Database Container], https://doi.org/10.26650/EurJBiol.2019.0024


Vancouver

Cebrailoğlu N, Yıldız AB, Akkaya Ö, Özden Çiftçi Y. CRISPR-Cas: Removing Boundaries of the Nature. European Journal of Biology [Internet]. 27 Apr. 2024 [cited 27 Apr. 2024];78(2):157-164. Available from: https://doi.org/10.26650/EurJBiol.2019.0024 doi: 10.26650/EurJBiol.2019.0024


ISNAD

Cebrailoğlu, Nicat - Yıldız, AliBurak - Akkaya, Özlem - Özden Çiftçi, Yelda. CRISPR-Cas: Removing Boundaries of the Nature”. European Journal of Biology 78/2 (Apr. 2024): 157-164. https://doi.org/10.26650/EurJBiol.2019.0024



TIMELINE


Submitted20.06.2019
Accepted29.07.2019
Published Online06.12.2019

LICENCE


Attribution-NonCommercial (CC BY-NC)

This license lets others remix, tweak, and build upon your work non-commercially, and although their new works must also acknowledge you and be non-commercial, they don’t have to license their derivative works on the same terms.


SHARE




Istanbul University Press aims to contribute to the dissemination of ever growing scientific knowledge through publication of high quality scientific journals and books in accordance with the international publishing standards and ethics. Istanbul University Press follows an open access, non-commercial, scholarly publishing.