GENE EDITING EXPLAINED! - A comprehensive guide to the principles, methods and technologies!

An “In Depth” lecture on gene editing brought to you by Dr Adam West, College of Medical Veterinary and Life Sciences at the University of Glasgow, Scotland. https://www.gla.ac.uk/people/adamwest Time stamps: 3:41 Introduction 9:04 DNA repair pathways 17:20 Possible genome editing outcomes using sequence-specific nucleases 23:32 Zinc finger nucleases (ZFNs) 34:38 Transcription activator-like effector nucleases (TALENs) 44:09 CRISPR adaptive immune systems 50:01 Using CRISPR/Cas9 for genome editing 1:10:54 CRISPR specificity 1:35:52 Precision editing 1:40:00 Homology directed repair 1:44:19 Enzymatic base editing 1:47:20 Prime editing The presentation is primarily aimed at university students, researchers, clinicians and journalists interested in fields related to molecular biology and genetics. It is for education purposes only. Please leave a comment to let us know whether this was helpful to you and what you think we should cover next. We are a new channel so please give us a like and share our video on your social media if you think others should see it. We have a lot of content coming up, so please subscribe! More accessible presentations for a wide audience can be found in the “Explained Simply” section of this channel in the near future. Artwork is © Adam West with the exception of images and data taken from publications referenced in these slides. References to reviews and journal articles are denoted by circled numbers at the bottom right of the slides. Links to these numbered articles are listed below. We recommend these as your best way to begin further reading on this subject. Publication List 1. Wah et al. Nature. 1997 Jul 3;388(6637):97-100. https://doi.org/10.1038/40446. 2. Wah et al. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10564-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC27934/ 3. Ceccaldi R et al. Trends Cell Biol. 2016 Jan;26(1):52-64. https://doi.org/10.1016/j.tcb.2015.07.009 5. Wolfe SA et al. J Mol Biol. 1999 Feb 5;285(5):1917-34. https://doi.org/10.1006/jmbi.1998.2421 6. Wolfe SA et al. Annu Rev Biophys Biomol Struct. 2000;29:183-212. https://doi.org/10.1146/annurev.biophys.29.1.183 7. Klug A. Q Rev Biophys. 2010 Feb;43(1):1-21. https://doi.org/10.1017/S0033583510000089 8. Urnov FD et al. Nat Rev Genet. 2010 Sep;11(9):636-46. https://doi.org/10.1038/nrg2842 9. Carroll D. Genetics. 2011 Aug;188(4):773-82. https://doi.org/10.1534/genetics.111.131433 10. Kim H and Kim JS. Nat Rev Genet. 2014 May;15(5):321-34. https://doi.org/10.1038/nrg3686 12. Boch J and Bonas U. Annu Rev Phytopathol. 2010;48:419-36. https://doi.org/10.1146/annurev-phyto-080508-081936 13. Bogdanove AJ et al. Curr Opin Plant Biol. 2010 Aug;13(4):394-401. https://doi.org/10.1016/j.pbi.2010.04.010 14. Mak AN et al. Science. 2012 Feb 10;335(6069):716-9. https://doi.org/10.1126/science.1216211 15. Joung JK and Sander JD. Nat Rev Mol Cell Biol. 2013 Jan;14(1):49-55. https://doi.org/10.1038/nrm3486 16. Mussolino C and Cathomen T. Curr Opin Biotechnol. 2012 Oct;23(5):644-50. https://doi.org/10.1016/j.copbio.2012.01.013 17. Mali P et al. Nat Methods. 2013 Oct;10(10):957-63. https://doi.org/10.1038/nmeth.2649 19. Garside EL and MacMillan AM. Nat Biotechnol. 2014 Apr;32(4):338-40. https://doi.org/10.1038/nbt.2872 20. Nishimasu H et al. Cell. 2014 Feb 27;156(5):935-49. https://doi.org/10.1016/j.cell.2014.02.001 21. Hsu PD et al. Cell. 2014 Jun 5;157(6):1262-78. https://doi.org/10.1016/j.cell.2014.05.010 22. Hendel A et al. Trends Biotechnol. 2015 Feb;33(2):132-40. https://doi.org/10.1016/j.tibtech.2014.12.001 23. Liang X et al. J Biotechnol. 2015 Aug 20;208:44-53. https://doi.org/10.1016/j.jbiotec.2015.04.024 24. Brinkman EK et al. Nucleic Acids Res. 2014 Dec 16;42(22):e168. https://doi.org/10.1093/nar/gku936 25. Koo T et al. Mol Cells. 2015 Jun;38(6):475-81. https://doi.org/10.14348/molcells.2015.0103 30. Howden SE et al. Stem Cell Reports. 2016 Sep 13;7(3):508-517. https://doi.org/10.1016/j.stemcr.2016.07.001 31. Fu Y et al. Nat Biotechnol. 2014 Mar;32(3):279-284. https://doi.org/10.1038/nbt.2808 32. Slaymaker IM et al. Science. 2016 Jan 1;351(6268):84-8. https://doi.org/10.1126/science.aad5227 33. Kleinstiver BP et al. Nature. 2016 Jan 28;529(7587):490-5. https://doi.org/10.1038/nature16526 34. Komor AC et al. Cell. 2017 Jan 12;168(1-2):20-36. https://doi.org/10.1016/j.cell.2016.10.044 37. Hess GT et al. Mol Cell. 2017 Oct 5;68(1):26-43. https://doi.org/10.1016/j.molcel.2017.09.029 38. Gaudelli NM et al. Nature. 2017 Nov 23;551(7681):464-471. https://doi.org/10.1038/nature24644 39. Anzalone AV et al. Nature. 2019 Dec;576(7785):149-157. https://doi.org/10.1038/s41586-019-1711-4 Music credits “Go, Icarus! Go!” by The Whole Other “New Year” by Bad Snacks (YouTube Audio Library)