Genom-Editierung mit CRISPR/Cas9: Vorzeichen einer neuen Epoche der Medizin?

Abstract

The emergence of genome editing technologies can be regarded as one of the most groundbreaking revolutions in the history of science. Modern genome editing allows the introduction of precise mutations into the genome of virtually all cells and organisms without leaving any additional trace. Undoubtedly, genome editing with CRISPR/Cas9, often casually referred to as “genetic scissors”, will revolutionize medical research and development. However, at the same time it creates a great need for ethical considerations as it might hold risks for both people and the environment that cannot yet be fully assessed. While genome editing is already well established in laboratory research, clinical applications based on genome editing are close. For the first time, targeted corrections of genetic defects in somatic cells, stem cells as well as in the germ line appear technically feasible. This generates possible future scenarios that urgently require broad ethical and social discussions.

Mit einfachen Mitteln lassen sich inzwischen präzise Änderungen am Genom von Zellen und Organismen vornehmen. Die Technologie der Genom-Editierung ist in der Grundlagenforschung bereits fest etabliert – der Einzug der Methodik in die klinische Medizin steht kurz bevor. Diese Revolution der Wissenschaftsgeschichte macht eine breite ethische Diskussion unumgänglich.

Schlüsselwörter

Genom-Editierung - Genschere - CRISPR/Cas9 - Gentherapie - Bioethik

Key words

genome editing - CRISPR/Cas9 - gene therapy - base editing - bioethics

• Literatur

• 1 Jinek M, Chylinski K, Fonfara I. et al. A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity. Science 2012; 337: 816-821
• 2 Cho SW, Kim S, Kim JM. et al. Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nat Biotechnol 2013; 31: 230-232
• 3 Cong L, Ran FA, Cox D. et al. Multiplex genome engineering using CRISPR/Cas systems. Science 2013; 339: 819-823
• 4 Jinek M, East A, Cheng A. et al. RNA-programmed genome editing in human cells. eLife 2013; 2: e00471
• 5 Mali P, Yang L, Esvelt KM. et al. RNA-guided human genome engineering via Cas9. Science 2013; 339: 823-826
• 6 Urnov FD. Genome Editing B. C. (Before CRISPR): Lasting Lessons from the “Old Testament”. The CRISPR Journal 2018; 1: 34-46
• 7 Nishimasu H, Shi X, Ishiguro S. et al. Engineered CRISPR-Cas9 nuclease with expanded targeting space. Science 2018;
• 8 Ran FA, Hsu PD, Wright J. et al. Genome engineering using the CRISPR-Cas9 system. Nat Protoc 2013; 8: 2281-2308
• 9 Liang P, Xu Y, Zhang X. et al. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein & cell 2015; 6: 363-372
• 10 Ormond KE, Mortlock DP, Scholes DT. et al. Human Germline Genome Editing. The American Journal of Human Genetics 2017; 101: 167-176
• 11 Fogarty NME, McCarthy A, Snijders KE. et al. Genome editing reveals a role for OCT4 in human embryogenesis. Nature 2017; 550: 67-73
• 12 Ma H, Marti-Gutierrez N, Park SW. et al. Correction of a pathogenic gene mutation in human embryos. Nature 2017; 548: 413-419
• 13 Deutscher Ethikrat. Keimbahneingriffe am menschlichen Embryo: Deutscher Ethikrat fordert globalen politischen Diskurs und internationale Regulierung (2017). Im Internet: https://www.ethikrat.org/fileadmin/Publikationen/Ad-hoc-Empfehlungen/deutsch/empfehlung-keimbahneingriffe-am-menschlichen-embryo.pdf Stand: 24.09.2018
• 14 Gaudelli NM, Komor AC, Rees HA. et al. Programmable base editing of A*T to G*C in genomic DNA without DNA cleavage. Nature 2017; 551: 464-471
• 15 Kim K, Ryu SM, Kim ST. et al. Highly efficient RNA-guided base editing in mouse embryos. Nat Biotechnol 2017; 35: 435-437
• 16 Zafra MP, Schatoff EM, Katti A. et al. Optimized base editors enable efficient editing in cells, organoids and mice. Nat Biotechnol 2018; 36: 888-893
• 17 Scheufele DA, Xenos MA, Howell EL. et al. U. S. attitudes on human genome editing. Science 2017; 357: 553-554
• 18 Knott GJ, Doudna JA. CRISPR-Cas guides the future of genetic engineering. Science 2018; 361: 866
• 19 Fellmann C, Gowen BG, Lin PC. et al. Cornerstones of CRISPR-Cas in drug discovery and therapy. Nat Rev Drug Discov 2017; 16: 89-100
• 20 Murugan K, Babu K, Sundaresan R. et al. The Revolution Continues: Newly Discovered Systems Expand the CRISPR-Cas Toolkit. Mol Cell 2017; 68: 15-25
• 21 Wang C, Zhai X, Zhang X. et al. Gene-edited babies: Chinese Academy of Medical Sciences’ response and action. Lancet 2018;