Subscribe to RSS
DOI: 10.1055/s-0042-119205
Genome Editing Tools und ihr Einsatz in der experimentellen Augenheilkunde
Genome Editing Tools and their Application in Experimental OphthalmologyPublication History
eingereicht 05 August 2016
akzeptiert 06 October 2016
Publication Date:
23 January 2017 (online)
Zusammenfassung
Neue molekularbiologische Werkzeuge revolutionieren zurzeit die Genomchirurgie (genome editing) mit weitreichendem Einfluss auch auf die experimentelle Augenheilkunde. Neben den bereits etablierten Systemen wie den Zinkfingernukleasen (ZFN) oder Transcription-activator-like-Effector-Nukleasen (TALEN) sind es insbesondere die CRISPR-/Cas-Systeme (CRISPR: clustered regularly interspaced short palindromic repeats; Cas: CRISPR-associated), die überraschend einfach einen gezielten und präzisen Schnitt im Genom lebender Zellen ermöglichen. Dieser DNA-Doppelstrangbruch wird in der Zelle mittels NHEJ (non-homologous end joining) oder HDR (homology directed repair) repariert und kann ausgenutzt werden, um ein defektes Gen zu deaktivieren oder mithilfe einer korrekten Gensequenz zu reparieren. Die Genome-Editing-Technologie eröffnet damit bisher ungeahnte Möglichkeiten in der Grundlagenforschung, Biotechnologie, biomedizinischen Forschung bis hin zu ersten klinischen Anwendungen. Neurodegenerative Erkrankungen der Netzhaut stehen dabei aufgrund der guten Zugänglichkeit und des Immunprivilegs des Auges mit im Fokus des Interesses von Forschern und Firmen.
Abstract
New genome editing tools in molecular biology are revolutionising precise genome surgery and have greatly influenced experimental ophthalmology too. Aside from the commonly used nuclease-based platforms, such as the zinc-finger nucleases (ZFN) and transcription activator-like effector nucleases (TALEN), CRISPR/Cas systems, clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) genes, perform very efficiently in site-specific DNA cleavage within living cells. DNA double strand breaks (DSB) are repaired through two different conserved repair pathways: NHEJ (non-homologous end joining) and HDR (homology directed repair). By using the correct DNA templates, these repair pathways can be used to knock out defective genes or to repair mutations. Genome editing technology lays the ground for new strategies in basic science, biotechnology, and biomedical science, as well as clinical studies with genome editing. Therapeutic gene editing strategies are now concentrating on diseases in the retina, due to the comparatively easy accessibility of the eye and with local application in vivo.
-
Literatur
- 1 Bates M. The CRISPR Conundrum: As millions of dollars flow into developing the gene-editing tool, scientists continue to discover the technologyʼs potential and pitfalls. IEEE Pulse 2016; 7: 17-21
- 2 McNutt M. Breakthrough to genome editing. Science 2015; 350: 1445
- 3 [Anonymous] Method of the Year 2011. Nat Methods 2012; 9: 1
- 4 Schmitt MW, Kennedy SR, Salk JJ. et al. Detection of ultra-rare mutations by next-generation sequencing. Proc Natl Acad Sci U S A 2012; 109: 14508-14513
- 5 Lelieveld SH, Veltman JA, Gilissen C. Novel bioinformatic developments for exome sequencing. Hum Genet 2016; 135: 603-614
- 6 Chaitankar V, Karakülah G, Ratnapriya R. et al. Next generation sequencing technology and genomewide data analysis: perspectives for retinal research. Prog Retin Eye Res 2016; 55: 1-31
- 7 Preising M, Stieger K, Lorenz B. [Inherited ophthalmological disorders. Part 1: Genetic fundamentals and phenotypes]. Klin Monatsbl Augenheilkd 2014; 231: 177-189
- 8 Tiwari A, Bahr A, Bähr L. et al. Next generation sequencing based identification of disease-associated mutations in Swiss patients with retinal dystrophies. Sci Rep 2016; 6: 28755
- 9 Lipinski D, Thake M, MacLaren R. Clinical applications of retinal gene therapy. Prog Retin Eye Res 2013; 32: 22-47
- 10 Farrar GJ, Millington-Ward S, Chadderton N. et al. Gene-based therapies for dominantly inherited retinopathies. Gene Ther 2012; 19: 137-144
- 11 Cox DB, Platt RJ, Zhang F. Therapeutic genome editing: prospects and challenges. Nat Med 2015; 21: 121-131
- 12 Lieber M. The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem 2010; 79: 181-211
- 13 Jasin M, Haber JE. The democratization of gene editing: Insights from site-specific cleavage and double-strand break repair. DNA Repair (Amst) 2016; 44: 6-16
- 14 Gaj T, Gersbach CA, Barbas 3rd CF. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol 2013; 31: 397-405
- 15 Chandrasegaran S, Carroll D. Origins of programmable nucleases for genome engineering. J Mol Biol 2016; 428: 963-989
- 16 Klug A. The discovery of zinc fingers and their applications in gene regulation and genome manipulation. Annu Rev Biochem 2010; 79: 213-231
- 17 Guo J, Gaj T, Barbas 3rd CF. Directed evolution of an enhanced and highly efficient FokI cleavage domain for zinc finger nucleases. J Mol Biol 2010; 400: 96-107
- 18 Maeder ML, Thibodeu-Beganny S, Osiak A. et al. Rapid “open-source” engineering of customized zinc-finger nucleases for highly efficient gene modification. Mol Cell 2008; 31: 294-301
- 19 Sander JD, Dahlborg EJ, Goodwin MJ. et al. Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA). Nat Methods 2011; 8: 67-69
- 20 Pingoud A, Wilson G, Wende W. Type II restriction endonucleases – a historical perspective and more. Nucleic Acids Res 2014; 42: 7489-7527
- 21 Gabriel R, Lombardo A, Arens A. et al. An unbiased genome-wide analysis of zinc-finger nuclease specificity. Nat Biotechnol 2011; 29: 816-823
- 22 Miller JC, Holmes MC, Wang J. et al. An improved zinc-finger nuclease architecture for highly specific genome editing. Nat Biotechnol 2007; 25: 778-785
- 23 Urnov FD, Rebar EJ, Holmes MC. et al. Genome editing with engineered zinc finger nucleases. Nat Rev Genet 2010; 11: 636-646
- 24 Rahman SH, Maeder ML, Joung JK. et al. Zinc-finger nucleases for somatic gene therapy: the next frontier. Hum Gene Ther 2011; 22: 925-933
- 25 Yao J, Huang J, Zhao J. Genome editing revolutionize the creation of genetically modified pigs for modeling human diseases. Hum Genet 2016; 135: 1093-1105
- 26 Tebas P, Stein D, Tang WW. et al. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N Engl J Med 2014; 370: 901-910
- 27 Boch J, Bonas U. Xanthomonas AvrBs3 family-type III effectors: discovery and function. Annu Rev Phytopathol 2010; 48: 419-436
- 28 Boch J, Scholze H, Schornack S. et al. Breaking the code of DNA binding specificity of TAL-type III effectors. Science 2009; 326: 1509-1512
- 29 Schmid-Burgk J, Schmidt T, Hornung V. Ligation-independent cloning (LIC) assembly of TALEN genes. Methods Mol Biol 2015; 1239: 161-169
- 30 Reyon D, Tsai SQ, Khayter C. et al. FLASH assembly of TALENs for high-throughput genome editing. Nat Biotechnol 2012; 30: 460-465
- 31 Boissel S, Jarjour J, Astrakhan A. et al. megaTALs: a rare-cleaving nuclease architecture for therapeutic genome engineering. Nucleic Acids Res 2014; 42: 2591-2601
- 32 Gabsalilow L, Schierling B, Friedhoff P. et al. Site- and strand-specific nicking of DNA by fusion proteins derived from MutH and I-SceI or TALE repeats. Nucleic Acids Res 2013; 41: e83
- 33 Yanik M, Alzubi J, Lahaye T. et al. TALE-PvuII fusion proteins – novel tools for gene targeting. PLoS One 2013; 8: e82539
- 34 Maeder ML, Angstman JF, Richardson ME. et al. Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins. Nat Biotechnol 2013; 31: 1137-1142
- 35 Scott JN, Kupinski AP, Boyes J. Targeted genome regulation and modification using transcription activator-like effectors. FEBS J 2014; 281: 4583-4597
- 36 Kungulovski G, Jeltsch A. Epigenome editing: state of the art, concepts, and perspectives. Trends Genet 2015; 32: 101-113
- 37 Holkers M, Maggio I, Liu J. et al. Differential integrity of TALE nuclease genes following adenoviral and lentiviral vector gene transfer into human cells. Nucleic Acids Res 2013; 41: e63
- 38 Holkers M, Maggio I, Henriques SF. et al. Adenoviral vector DNA for accurate genome editing with engineered nucleases. Nat Methods 2014; 11: 1051-1057
- 39 Qasim W, Amrolia PJ, Samarasinghe S. et al. First clinical application of talen engineered universal CAR19 T Cells in B-ALL. Blood 2015; 126: 2046
- 40 Reardon S. Leukaemia success heralds wave of gene-editing therapies. Nature 2015; 527: 146-147
- 41 Roberts RJ. How restriction enzymes became the workhorses of molecular biology. Proc Natl Acad Sci U S A 2005; 102: 5905-5908
- 42 Doudna JA, Charpentier E. Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science 2014; 346: 1258096
- 43 Cong L, Ran FA, Cox D. et al. Multiplex genome engineering using CRISPR/Cas systems. Science 2013; 339: 819-823
- 44 Horvath P, Barrangou R. CRISPR/Cas, the immune system of bacteria and archaea. Science 2010; 327: 167-170
- 45 Jinek M, Chylinski K, Fonfara I. et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 2012; 337: 816-821
- 46 Mali P, Yang L, Esvelt KM. et al. RNA-guided human genome engineering via Cas9. Science 2013; 339: 823-826
- 47 Jinek M, East A, Cheng A. et al. RNA-programmed genome editing in human cells. Elife 2013; 2: e00471
- 48 Haeussler M, Concordet JP. Genome editing with CRISPR-Cas9: can it get any better?. J Genet Genomics 2016; 43: 239-250
- 49 Ran FA, Cong L, Yan WX. et al. In vivo genome editing using Staphylococcus aureus Cas9. Nature 2015; 520: 186-191
- 50 Kleinstiver BP, Prew MS, Tsai SQ. et al. Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition. Nat Biotechnol 2015; 33: 1293-1298
- 51 Doench JG, Fusi N, Sullender M. et al. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9. Nat Biotechnol 2016; 34: 184-191
- 52 Gabriel R, von Kalle C, Schmidt M. Mapping the precision of genome editing. Nat Biotechnol 2015; 33: 150-152
- 53 Fu Y, Sander JD, Reyon D. et al. Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat Biotechnol 2014; 32: 279-284
- 54 Ran FA, Hsu PD, Lin CY. et al. Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell 2013; 154: 1380-1389
- 55 Tsai SQ, Wyvekens N, Khayter C. et al. Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing. Nat Biotechnol 2014; 32: 569-576
- 56 Slaymaker IM, Gao L, Zetsche B. et al. Rationally engineered Cas9 nucleases with improved specificity. Science 2016; 351: 84-88
- 57 Kleinstiver BP, Pattanayak V, Prew MS. et al. High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature 2016; 529: 490-495
- 58 Corrigan-Curay J, OʼReilly M, Kohn DB. et al. Genome editing technologies: defining a path to clinic. Mol Ther 2015; 23: 796-806
- 59 Yee JK. Off-target effects of engineered nucleases. FEBS J 2016; 283: 3239-3248
- 60 Mei Y, Wang Y, Chen H. et al. Recent progress in CRISPR/Cas9 technology. J Genet Genomics 2016; 43: 63-75
- 61 Yang L, Güell M, Niu D. et al. Genome-wide inactivation of porcine endogenous retroviruses (PERVs). Science 2015; 350: 1101-1104
- 62 Liang P, Xu Y, Zhang X. et al. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell 2015; 6: 363-372
- 63 Lanphier E, Urnov F, Haecker SE. et al. Donʼt edit the human germ line. Nature 2015; 519: 410-411
- 64 Baltimore D, Berg P, Botchan M. et al. A prudent path forward for genomic engineering and germline gene modification. Science 2015; 348: 36-38
- 65 Stoddard BL, Fox K. Editorial: CRISPR in nucleic acids research. Nucleic Acids Res 2016; 44: 4989-4990
- 66 Hung SS, McCaughey T, Swann O. et al. Genome engineering in ophthalmology: application of CRISPR/Cas to the treatment of eye disease. Prog Retin Eye Res 2016; 53: 1-20
- 67 Berger W, Kloeckener-Gruissem B, Neidhardt J. The molecular basis of human retinal and vitreoretinal diseases. Prog Retin Eye Res 2010; 29: 335-375
- 68 Petit L, Khanna H, Punzo C. Advances in gene therapy for diseases of the eye. Hum Gene Ther 2016; 27: 563-579
- 69 Boye SE, Boye SL, Lewin AS. et al. A comprehensive review of retinal gene therapy. Mol Ther 2013; 21: 509-519
- 70 Schimmer J, Breazzano S. Investor outlook: significance of the positive LCA2 gene therapy phase III results. Hum Gene Ther Clin Dev 2015; 26: 208-210
- 71 Cox DB, Platt RJ, Zhang F. Therapeutic genome editing: prospects and challenges. Nat Med 2015; 21: 121-131
- 72 Yanik M, Müller B, Song F. et al. In vivo genome editing as a potential treatment strategy for inherited retinal dystrophies. Prog Retin Eye Res 2016;
- 73 Wiley LA, Burnight ER, Songstad AE. et al. Patient-specific induced pluripotent stem cells (iPSCs) for the study and treatment of retinal degenerative diseases. Prog Retin Eye Res 2015; 44: 15-35