2016 / 03

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DOI: 10.24075/brsmu.2016-03-01

REVIEW

Human genome editing

Rebrikov DV1,2,3
About authors

1 Pirogov Russian National Research Medical University, Moscow, Russia

2 Kulakov Federal Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia

3 Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia

Correspondence should be addressed: Denis V. Rebrikov
ul. Ostrovityanova, d. 1, Moscow, Russia, 117997; moc.liamg@vokirberd

Received: 2016-06-23 Accepted: 2016-06-25 Published online: 2017-01-05
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  1. Friedmann T, Roblin R. Gene Therapy for Human Genetic Disease? Science. 1972; 175 (4025): 949–55. DOI:10.1126/science.175.4025.949.
  2. Rosenberg SA, Aebersold P, Cornetta K, Kasid A, Morgan RA, Moen R, et al. Gene transfer into humans--immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med. 1990 Aug 30; 323 (9): 570–8. DOI:10.1056/NEJM199008303230904.
  3. Gene Therapy Clinical Trials Worldwide Database [Internet]. John Wiley and Sons Ltd., provided by the Journal of Gene Medicine. c2016 – [updated 2016 Feb; cited 2016 Jun]. Available from: http://www.wiley.com/legacy/wileychi/genmed/clinical/.
  4. De Ravin SS, Wu X, Moir S, Anaya-O'Brien S, Kwatemaa N, Little P, et al. Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency. Sci Transl Med. 2016 Apr 20; 8 (335): 335ra57. DOI: 10.1126/scitranslmed.aad8856.
  5. Ward P, Walsh CE. Current and future prospects for hemophilia gene therapy. Expert Rev Hematol. 2016 May 26: 1–11. [Epub ahead of print].
  6. Swystun LL, Lillicrap D. Gene Therapy for Coagulation Disorders. Circ Res. 2016 Apr 29; 118 (9): 1443–52. DOI: 10.1161/CIRCRESAHA.115.307015.
  7. Liang P, Xu Y, Zhang X, Ding C, Huang R, Zhang Z, et al. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell. 2015 May; 6 (5): 363–72. DOI: 10.1007/s13238-015-0153-5. Epub 2015 Apr 18.
  8. Canver MC, Orkin SH. Customizing the genome as therapy for the β-hemoglobinopathies. Blood. 2016 May 26; 127 (21): 2536–45. DOI: 10.1182/blood-2016-01-678128. Epub 2016 Apr 6.
  9. Cottle RN, Lee CM, Bao G. Treating hemoglobinopathies using gene-correction approaches: promises and challenges. Hum Genet. 2016 Jun 17. [Epub ahead of print].
  10. Tasan I, Jain S, Zhao H. Use of genome-editing tools to treat sickle cell disease. Hum Genet. 2016 Jun 1. [Epub ahead of print].
  11. Osborn MJ, Belanto JJ, Tolar J, Voytas DF. Gene editing and its application for hematological diseases. Int J Hematol. 2016 May 27. [Epub ahead of print].
  12. Yang Y, Zhang X, Yi L, Hou Z, Chen J, Kou X, et al. Naïve Induced Pluripotent Stem Cells Generated From β-Thalassemia Fibroblasts Allow Efficient Gene Correction With CRISPR/Cas9. Stem Cells Transl Med. 2016 Jan; 5 (1): 8–19. DOI: 10.5966/sctm.2015-0157. Epub 2015 Dec 16. Erratum in: Stem Cells Transl Med. 2016 Feb; 5 (2): 267.
  13. Smith EC, Orkin SH. Hemoglobin genetics: recent contributions of GWAS and gene editing. Hum Mol Genet. 2016 Jun 23. pii: ddw170. [Epub ahead of print].
  14. Lee TW, Southern KW, Perry LA, Penny-Dimri JC, Aslam AA. Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease. Cochrane Database Syst Rev. 2016 Jun 17; 6: CD005599.
  15. Alton EW, Armstrong DK, Ashby D, Bayfield KJ, Bilton D, Bloomfield EV, et al. Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Respir Med. 2015 Sep; 3 (9): 684–91. DOI:10.1016/S2213-2600(15)00245-3.
  16. Ye GJ, Budzynski E, Sonnentag P, Nork TM, Sheibani N, Gurel Z, et al. Cone-Specific Promoters for Gene Therapy of Achromatopsia and Other Retinal Diseases. Hum Gene Ther. 2016 Jan; 27 (1): 72–82. DOI: 10.1089/hum.2015.130.
  17. Maguire AM, Simonelli F, Pierce EA, Pugh EN, Mingozzi F, Bennicelli J, et al. Safety and efficacy of gene transfer for Leber's congenital amaurosis. N Engl J Med. 2008; 358 (21): 2240–8. DOI:10.1056/NEJMoa0802315.
  18. Bainbridge JWB, Smith AJ, Barker SS, Robbie S, Henderson R, Balaggan K, et al. Effect of gene therapy on visual function in Leber's congenital amaurosis. N Engl J Med. 2008; 358 (21): 2231–9. DOI:10.1056/NEJMoa0802268.
  19. Hauswirth WW, Aleman TS, Kaushal S, Cideciyan AV, Schwartz SB, Wang L, et al. Treatment of Leber Congenital Amaurosis Due to RPE65Mutations by Ocular Subretinal Injection of Adeno-Associated Virus Gene Vector: Short-Term Results of a Phase I Trial. Hum Gene Ther. 2008 Oct; 19 (10): 979–90. DOI:10.1089/hum.2008.107.
  20. Walker MC, Schorge S, Kullmann DM, Wykes RC, Heeroma JH, Mantoan L. Gene therapy in status epilepticus. Epilepsia. 2013 Sep; 54 Suppl 6: 43–5. DOI:10.1111/epi.12275.
  21. Giuncamp C, Pap T, Schedel J, Pap G, Moller-Ladner U, Gay RE, Gay S. Gene therapy in osteoarthritis. Joint Bone Spine. 2000; 67 (6): 570–1.
  22. Evans CH, Gouze JN, Gouze E, Robbins PD, Ghivizzani SG. Osteoarthritis gene therapy. Gene Ther. 2004 Feb; 11 (4): 379–89. DOI: 10.1038/sj.gt.3302196.
  23. Carlsson T, Winkler C, Burger C, Muzyczka N, Mandel RJ, Cenci A, et al. Reversal of dyskinesias in an animal model of Parkinson's disease by continuous L-DOPA delivery using rAAV vectors. Brain. 2005 Mar; 128 (Pt 3): 559–69. DOI: 10.1093/brain/awh374.
  24. Forsayeth J, Bankiewicz KS, Aminoff MJ. Gene therapy for Parkinson's disease: Where are we now and where are we going? Expert Rev Neurother. 2010 Dec; 10 (12): 1839–45. DOI: 10.1586/ern.10.161.
  25. Palfi S, Gurruchaga, JM, Ralph GS, Lepetit H, Lavisse S, Buttery PC, et al. Long-term safety and tolerability of Pro Savin, a lentiviral vector-based gene therapy for Parkinson's disease: A dose escalation, open-label, phase 1/2 trial. Lancet. 2014 Mar 29; 383 (9923): 1138–46. DOI: 10.1016/S0140-6736(13)61939-X.
  26. Cross D, Burmester JK. Gene Therapy for Cancer Treatment: Past, Present and Future. Clin Med Res. 2006 Sep; 4 (3): 218–27.
  27. Andersen JB, Thorgeirsson SS. A perspective on molecular therapy in cholangiocarcinoma: present status and future directions. Hepat Oncol. 2014 Jan 1; 1 (1): 143–57.
  28. Amer MH. Gene therapy for cancer: present status and future perspective. Mol Cell Ther. 2014 Sep 10; 2: 27. DOI: 10.1186/2052-8426-2-27.
  29. Khan FA, Pandupuspitasari NS, Chun-Jie H, Ao Z, Jamal M, Zohaib A, et al. CRISPR/Cas9 therapeutics: a cure for cancer and other genetic diseases. Oncotarget. 2016 May 26. DOI: 10.18632/oncotarget.9646. [Epub ahead of print].
  30. White MK, Khalili K. CRISPR/Cas9 and cancer targets: future possibilities and present challenges. Oncotarget. 2016 Mar 15; 7 (11): 12305–17. DOI: 10.18632/oncotarget.7104.
  31. Liu T, Shen JK, Li Z, Choy E, Hornicek FJ, Duan Z. Development and potential applications of CRISPR-Cas9 genome editing technology in sarcoma. Cancer Lett. 2016 Apr 1; 373 (1): 109–18. DOI: 10.1016/j.canlet.2016.01.030. Epub 2016 Jan 21.
  32. Tang H, Shrager JB. CRISPR/Cas-mediated genome editing to treat EGFR-mutant lung cancer: a personalized molecular surgical therapy. EMBO Mol Med. 2016 Jan 8; 8 (2): 83–5. DOI: 10.15252/emmm.201506006.
  33. Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J. Chapter 8.5: Gene Replacement and Transgenic Animals: DNA Is Transferred into Eukaryotic Cells in Various Ways. In: Molecular Cell Biology. 4th ed. New York: W. H. Freeman; 2002. ISBN 0-7167-3136-3.
  34. O'Gorman S, Fox DT, Wahl GM. Recombinase-mediated gene activation and site-specific integration in mammalian cells. Science. 1991 Mar 15; 251 (4999): 1351–5. DOI: 10.1126/science.1900642.
  35. Karow M, Calos MP. The therapeutic potential of phiC31 integrase as a gene therapy system. Expert Opin Biol Ther. 2011 Oct; 11 (10): 1287–96. DOI:10.1517/14712598.2011.601293.
  36. Pabo CO, Peisach E, Grant RA. Design and Selection of Novel Cys2His2 Zinc Finger Proteins. Annu. Rev Biochem. 2001; 70: 313–40.
  37. Maeder ML, Thibodeau-Beganny S, Osiak A, Wright DA, Anthony RM, Eichtinger M, et al. Rapid "open-source" engineering of customized zinc-finger nucleases for highly efficient gene modification. Mol Cell. 2008 Jul 25; 31 (2): 294–301. DOI: 10.1016/j.molcel.2008.06.016.
  38. Carroll D. Genome engineering with zinc-finger nucleases. Genetics. 2011 Aug; 188 (4): 773–82. DOI: 10.1534/genetics.111.131433.
  39. Epinat JC, Arnould S, Chames P, Rochaix P, Desfontaines D, Puzin C, et al. A novel engineered meganuclease induces homologous recombination in yeast and mammalian cells. Nucleic Acids Res. 2003 Jun 1; 31 (11): 2952–62. DOI: 10.1093/nar/gkg375.
  40. Boch J. TALEs of genome targeting. Nat Biotechnol. 2011 Feb; 29 (2): 135–6. DOI: 10.1038/nbt.1767.
  41. Mali P, Esvelt KM, Church GM. Cas9 as a versatile tool for engineering biology. Nat Methods. 2013 Oct; 10 (10): 957–63. DOI: 10.1038/nmeth.2649.
  42. Boissel S, Jarjour J, Astrakhan A, Adey A, Gouble A, Duchateau P, et al. megaTALs: a rare-cleaving nuclease architecture for therapeutic genome engineering. Nucleic Acids Res. 2014 Feb; 42 (4): 2591–601. DOI: 10.1093/nar/gkt1224.
  43. Certo MT, Gwiazda KS, Kuhar R, Sather B, Curinga G, Mandt T, et al. Coupling endonucleases with DNA end-processing enzymes to drive gene disruption. Nat Methods. 2012 Oct; 9 (10): 973–5. DOI: 10.1038/nmeth.2177.
  44. Delacôte F, Perez C, Guyot V, Duhamel M, Rochon C, Ollivier N, et al. High frequency targeted mutagenesis using engineered endonucleases and DNA-end processing enzymes. PLoS One. 2013; 8 (1): e53217. DOI: 10.1371/journal.pone.0053217.
  45. Doudna JA, Charpentier E. The new frontier of genome engineering with CRISPR-Cas9. Science. 2014 Nov 28; 346 (6213): 1258096. DOI: 10.1126/science.1258096
  46. Nemudriy AA, Valetdinova KR, Medvedev SP, Zakiyan SM. Sistemy redaktirovaniya genomov TALEN i CRISPR/Cas — instrumenty otkrytiy. Acta naturae. 2014; vol. 6, 3 (22): 20–41.
  47. Yin H, Kanasty RL, Eltoukhy AA, Vegas AJ, Dorkin JR, Anderson DG. Non-viral vectors for gene-based therapy. Nat Rev Genet. 2014 Aug; 15 (8): 541–55. DOI: 10.1038/nrg3763. Epub 2014 Jul 15.
  48. Kim YG, Cha J, Chandrasegaran S. Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proc Natl Acad Sci U S A. 1996 Feb 6; 93 (3): 1156–60.
  49. Pattanayak V, Ramirez CL, Joung JK, Liu DR. Revealing Off-Target Cleavage Specificities of Zinc Finger Nucleases by in Vitro Selection. Nat Methods, 2011 Aug 7; 8 (9): 765–70. DOI: 10.1038/nmeth.1670.
  50. Wood AJ, Lo TW, Zeitler B, Pickle CS, Ralston EJ, Lee AH, et al. Targeted Genome Editing Across Species Using ZFNs and TALENs. Science. 2011 Jul 15; 333 (6040): 307. DOI: 10.1126/science.1207773.
  51. Boch J, Scholze H, Schornack S, Landgraf A, Hahn S, Kay S, et al. Breaking the Code of DNA Binding Specificity of TAL-Type III Effectors. Science. 2009 Dec 11; 326 (5959): 1509–12. DOI: 10.1126/science.1178811.
  52. Moscou MJ, Bogdanove AJ. A Simple Cipher Governs DNA Recognition by TAL Effectors. Science. 2009 Dec 11; 326 (5959): 1501. Bibcode:2009Sci...326.1501M. DOI:10.1126/science.1178817. PMID 19933106.
  53. Horvath P, Barrangou R (January 2010). "CRISPR/Cas, the immune system of bacteria and archaea". Science 327 (5962): 167–70. DOI: 10.1126/Science.1179555.
  54. Swarts DC, Mosterd C, van Passel MW, Brouns SJ. CRISPR interference directs strand specific spacer acquisition. PloS One. 2012; 7 (4): e35888. DOI: 10.1371/journal.pone.0035888.
  55. Boroviak K, Doe B, Banerjee R, Yang F, Bradley A. Chromosome engineering in zygotes with CRISPR/Cas9. Genesis. 2016 Feb; 54 (2): 78–85. DOI: 10.1002/dvg.22915. Epub 2016 Jan 25.
  56. Yin H, Song CQ, Dorkin JR, Zhu LJ, Li Y, Wu Q, et al. Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo. Nat Biotechnol. 2016 Mar; 34 (3): 328–33. DOI: 10.1038/nbt.3471. Epub 2016 Feb 1.
  57. End of chemotherapy within 20 years as pioneering DNA project launched. The Daily Telegraph, 01.08.2014
  58. Zhu W, Xie K, Xu Y, Wang L, Chen K, Zhang L, Fang J. CRISPR/Cas9 produces anti-hepatitis B virus effect in hepatoma cells and transgenic mouse. Virus Res. 2016 Jun 2; 217: 125–32. DOI: 10.1016/j.virusres.2016.04.003. Epub 2016 Apr 2.
  59. Hung SS, McCaughey T, Swann O, Pébay A, Hewitt AW. Genome engineering in ophthalmology: Application of CRISPR/Cas to the treatment of eye disease. Prog Retin Eye Res. 2016 Jun; 53; 1–20. DOI: 10.1016/j.preteyeres.2016.05.001. [Epub ahead of print].
  60. Bassuk AG, Zheng A, Li Y, Tsang SH, Mahajan VB. Precision Medicine: Genetic Repair of Retinitis Pigmentosa in Patient-Derived Stem Cells. Sci Rep. 2016 Jan 27; 6:19969. DOI: 10.1038/srep19969.
  61. Nafissi N, Foldvari M. Neuroprotective therapies in glaucoma: II. Genetic nanotechnology tools. Front Neurosci. 2015 Oct 14; 9: 355. DOI: 10.3389/fnins.2015.00355.
  62. Li Y, Chan L, Nguyen HV, Tsang SH. Personalized Medicine: Cell and Gene Therapy Based on Patient-Specific iPSC-Derived Retinal Pigment Epithelium Cells. Adv Exp Med Biol. 2016; 854: 549–55. DOI: 10.1007/978-3-319-17121-0_73
  63. Wu WH, Tsai YT, Justus S, Lee T, Zhang L, Lin CS, et al. CRISPR repair reveals causative mutation in a preclinical model of retinitis pigmentosa. Mol Ther. 2016 May 20. DOI: 10.1038/mt.2016.107. [Epub ahead of print].
  64. Mendell JR, Rodino-Klapac LR. Duchenne muscular dystrophy: CRISPR/Cas9 treatment. Cell Res. 2016 May; 26 (5): 513–4. DOI: 10.1038/cr.2016.28. Epub 2016 Mar 1.
  65. Himeda CL, Jones TI, Jones PL. Scalpel or Straitjacket: CRISPR/Cas9 Approaches for Muscular Dystrophies. Trends Pharmacol Sci. 2016 Apr; 37 (4): 249–51. DOI: 10.1016/j.tips.2016.02.001. Epub 2016 Feb 22.
  66. Iyombe-Engembe JP, Ouellet DL, Barbeau X, Rousseau J, Chapdelaine P, Lagüe P, Tremblay JP. Efficient Restoration of the Dystrophin Gene Reading Frame and Protein Structure in DMD Myoblasts Using the CinDel Method. Mol Ther Nucleic Acids. 2016 Jan 26; 5: e283. DOI: 10.1038/mtna.2015.58.
  67. Maggio I, Stefanucci L, Janssen JM, Liu J, Chen X, Mouly V, Gonçalves MA. Selection-free gene repair after adenoviral vector transduction of designer nucleases: rescue of dystrophin synthesis in DMD muscle cell populations. Nucleic Acids Res. 2016 Feb 18; 44 (3): 1449–70. DOI: 10.1093/nar/gkv1540. Epub 2016 Jan 13.
  68. Kawecka K, Theodoulides M, Hasoglu Y, Jarmin S, Kymalainen H, Le-Heron A, et al. Adeno-Associated Virus (AAV) Mediated Dystrophin Gene Transfer Studies and Exon Skipping Strategies for Duchenne Muscular Dystrophy (DMD). Curr Gene Ther. 2015; 15 (4): 395–415.
  69. Ousterout DG, Kabadi AM, Thakore PI, Majoros WH, Reddy TE, Gersbach CA. Multiplex CRISPR/Cas9-based genome editing for correction of dystrophin mutations that cause Duchenne muscular dystrophy. Nat Commun. 2015 Feb 18; 6: 6244. DOI: 10.1038/ncomms7244.
  70. Ousterout DG, Kabadi AM, Thakore PI, Perez-Pinera P, Brown MT, Majoros WH, et al. Correction of dystrophin expression in cells from Duchenne muscular dystrophy patients through genomic excision of exon 51 by zinc finger nucleases. Mol Ther. 2015 Mar; 23 (3): 523–32. DOI: 10.1038/mt.2014.234. Epub 2014 Dec 10.
  71. Maggio I, Chen X, Gonçalves MA. The emerging role of viral vectors as vehicles for DMD gene editing. Genome Med. 2016 May 23; 8 (1): 59. DOI: 10.1186/s13073-016-0316-x.
  72. Reardon S. Gene-editing method tackles HIV in first clinical test. Nature. 2014 Mar 05. DOI: 10.1038/nature.2014.14813.
  73. Tebas P, Stein D, Tang WW, Frank I, Wang SQ, Lee G, et al. Gene Editing of CCR5 in Autologous CD4 T Cells of Persons Infected with HIV. N Engl J Med. 2014 Mar 6; 370 (10): 901–10. DOI: 10.1056/NEJMoa1300662.
  74. Kaminski R, Bella R, Yin C, Otte J, Ferrante P, Gendelman HE, et al. Excision of HIV-1 DNA by gene editing: a proof-of-concept in vivo study. Gene Ther. 2016 May 19. DOI: 10.1038/gt.2016.41. [Epub ahead of print].
  75. Ueda S, Ebina H, Kanemura Y, Misawa N, Koyanagi Y. Insufficient anti-HIV-1 potency of the CRISPR/Cas9 system for full viral replication. Microbiol Immunol. 2016 Jun 9. DOI: 10.1111/1348-0421.12395. [Epub ahead of print].
  76. Stone D, Niyonzima N, Jerome KR. Genome editing and the next generation of antiviral therapy. Hum Genet. 2016 Jun 8. [Epub ahead of print].
  77. Pernet O, Yadav SS, An DS. Stem cell-based therapies for HIV/AIDS. Adv Drug Deliv Rev. 2016 May 2. pii: S0169–409X(16)30137–5. DOI: 10.1016/j.addr.2016.04.027. [Epub ahead of print].
  78. Kim M, Siliciano RF. Genome editing for clinical HIV isolates. Nat Biotechnol. 2016 Apr 7; 34 (4): 388–9. DOI: 10.1038/nbt.3531.
  79. Wang CX, Cannon PM. The clinical applications of genome editing in HIV. Blood. 2016 May 26; 127 (21): 2546–52. DOI: 10.1182/blood-2016-01-678144. Epub 2016 Apr 6.
  80. Wang Z, Pan Q, Gendron P, Zhu W, Guo F, Cen S, et al. CRISPR/Cas9-Derived Mutations Both Inhibit HIV-1 Replication and Accelerate Viral Escape. Cell Rep. 2016 Apr 19; 15 (3): 481–9. DOI: 10.1016/j.celrep.2016.03.042. Epub 2016 Apr 7.
  81. Wang G, Zhao N, Berkhout B, Das AT. CRISPR-Cas9 Can Inhibit HIV-1 Replication but NHEJ Repair Facilitates Virus Escape. Mol Ther. 2016 Mar; 24 (3): 522–6. DOI: 10.1038/mt.2016.24. Epub 2016 Jan 22.
  82. Kaminski R, Chen Y, Fischer T, Tedaldi E, Napoli A, Zhang Yet al. Elimination of HIV-1 Genomes from Human T-lymphoid Cells by CRISPR/Cas9 Gene Editing. Sci Rep. 2016 Mar 4; 6: 22555. DOI: 10.1038/srep22555.
  83. Momaya A, Fawal M, Estes R. Performance-enhancing substances in sports: a review of the literature. Sports Med. 2015 Apr; 45 (4): 517–31. DOI: 10.1007/s40279-015-0308-9.
  84. World Anti-Doping Agency. The World Anti-Doping Code: The 2015 Prohibited List of International Standards. Montreal (Quebec); 2014 Sep 20. 10 p.
  85. Adis Insight [Internet]. Cham (Switzerland): Springer International Publishing AG; [cited 2016 Jun]. Drug Profile: Erythropoietin gene therapy — Oxford BioMedica. Available from: http://adisinsight.springer.com/drugs/800017416.
  86. Barry P. Finding the golden genes. Science News. 2008 Jul 18.
  87. Miah A. Genetically Modified Athletes: Biomedical Ethics, Gene Doping and Sport. London; New York: Routledge; 2004. 208 p.
  88. Regalado A. Engineering the Perfect Baby. MIT Technology Review. 2015 Mar 5.
  89. Parens E, Knowles LP. Reprogenetics and public policy. Reflections and recommendations. Hastings Cent Rep. 2003 Jul–Aug; 33 (4): S1–24.
  90. Pray L. Embryo screening and the ethics of human genetic engineering. Nature Education. 2008; 1 (1): 207.
  91. Ahmetov II, Egorova ES, Gabdrakhmanova LJ, Fedotovskaya ON. Genes and Athletic Performance: An Update. Med Sport Sci. 2016; 61: 41–54. DOI: 10.1159/000445240. Epub 2016 Jun 10.
  92. Baltimore D, Berg P, Botchan M, Carroll D, Charo RA, Church G, et al. A prudent path forward for genomic engineering and germline gene modification. Science. 2015 Apr 3; 348  (6230): 36–3. DOI: 10.1126/science.aab1028.
  93. Knapton S. British scientists granted permission to genetically modify human embryos. The Daily Telegraph. 2016 Feb 1.