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Genome Editing for Duchenne Muscular Dystrophy

  • Christopher E. Nelson
  • Charles A. GersbachEmail author
Chapter

Abstract

The recent genome editing revolution has been fueled by the discovery and adaptation of highly specific endonucleases including meganucleases, zinc finger nucleases (ZFNs), TALENs, and CRISPR/Cas9. These genome editing technologies permit user-defined genome modifications by creating double-strand DNA breaks and exploiting endogenous DNA repair pathways to introduce DNA sequence changes. Genome editing has entered multiple clinical trials in a range of diseases including HIV, cancer, and hemophilia, and several preclinical successes have been reported for treating models of neuromuscular diseases, including Duchenne muscular dystrophy (DMD). These studies include correction of numerous different mutations in patient-derived muscle cells and stem cells by a variety of genome editing strategies and endonuclease technologies. Preclinical studies have also shown efficacy of genome editing by restoring dystrophin protein expression and improving skeletal muscle physiology in animal models of DMD. This preclinical work highlights the potential for DNA repair therapy to treat DMD and other debilitating and fatal genetic diseases. Ongoing work seeks to address remaining issues including efficient delivery, addressing potential immune response or off-target interactions, and characterizing long-term safety and efficacy.

Keywords

DNA repair Genome editing CRISPR/Cas9 DMD AAV Adenovirus 

References

  1. 1.
    Monaco AP, Neve RL, Colletti-Feener C, Bertelson CJ, Kurnit DM, Kunkel LM (1986) Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene. Nature 323(6089):646–650.  https://doi.org/10.1038/323646a0 CrossRefPubMedGoogle Scholar
  2. 2.
    Hoffman EP, Brown RH Jr, Kunkel LM (1987) Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51(6):919–928CrossRefGoogle Scholar
  3. 3.
    Fairclough RJ, Wood MJ, Davies KE (2013) Therapy for Duchenne muscular dystrophy: renewed optimism from genetic approaches. Nat Rev Genet 14(6):373–378.  https://doi.org/10.1038/nrg3460 CrossRefPubMedGoogle Scholar
  4. 4.
    Gaj T, Gersbach CA, Barbas CF 3rd (2013) ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol 31(7):397–405.  https://doi.org/10.1016/j.tibtech.2013.04.004 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Maeder ML, Gersbach CA (2016) Genome-editing Technologies for Gene and Cell Therapy. Mol Ther 24(3):430–446.  https://doi.org/10.1038/mt.2016.10 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Stoddard BL (2011) Homing endonucleases: from microbial genetic invaders to reagents for targeted DNA modification. Structure 19(1):7–15.  https://doi.org/10.1016/j.str.2010.12.003 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Gersbach CA, Gaj T, Barbas CF 3rd (2014) Synthetic zinc finger proteins: the advent of targeted gene regulation and genome modification technologies. Acc Chem Res 47(8):2309–2318.  https://doi.org/10.1021/ar500039w CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD (2010) Genome editing with engineered zinc finger nucleases. Nat Rev Genet 11(9):636–646.  https://doi.org/10.1038/nrg2842 CrossRefPubMedGoogle Scholar
  9. 9.
    Bogdanove AJ, Voytas DF (2011) TAL effectors: customizable proteins for DNA targeting. Science 333(6051):1843–1846.  https://doi.org/10.1126/science.1204094 CrossRefPubMedGoogle Scholar
  10. 10.
    Hsu PD, Lander ES, Zhang F (2014) Development and applications of CRISPR-Cas9 for genome engineering. Cell 157(6):1262–1278.  https://doi.org/10.1016/j.cell.2014.05.010 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Taghian DG, Nickoloff JA (1997) Chromosomal double-strand breaks induce gene conversion at high frequency in mammalian cells. Mol Cell Biol 17(11):6386–6393CrossRefGoogle Scholar
  12. 12.
    Shrivastav M, De Haro LP, Nickoloff JA (2008) Regulation of DNA double-strand break repair pathway choice. Cell Res 18(1):134–147.  https://doi.org/10.1038/cr.2007.111 CrossRefPubMedGoogle Scholar
  13. 13.
    Lieber MR (2010) The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem 79:181–211.  https://doi.org/10.1146/annurev.biochem.052308.093131 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Santiago Y, Chan E, Liu PQ, Orlando S, Zhang L, Urnov FD, Holmes MC, Guschin D, Waite A, Miller JC, Rebar EJ, Gregory PD, Klug A, Collingwood TN (2008) Targeted gene knockout in mammalian cells by using engineered zinc-finger nucleases. Proc Natl Acad Sci U S A 105(15):5809–5814.  https://doi.org/10.1073/pnas.0800940105 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Lee HJ, Kim E, Kim JS (2010) Targeted chromosomal deletions in human cells using zinc finger nucleases. Genome Res 20(1):81–89.  https://doi.org/10.1101/gr.099747.109 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Sollu C, Pars K, Cornu TI, Thibodeau-Beganny S, Maeder ML, Joung JK, Heilbronn R, Cathomen T (2010) Autonomous zinc-finger nuclease pairs for targeted chromosomal deletion. Nucleic Acids Res 38(22):8269–8276.  https://doi.org/10.1093/nar/gkq720 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Hilton IB, Gersbach CA (2015) Enabling functional genomics with genome engineering. Genome Res 25(10):1442–1455.  https://doi.org/10.1101/gr.190124.115 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Thakore PI, Black JB, Hilton IB, Gersbach CA (2016) Editing the epigenome: technologies for programmable transcription and epigenetic modulation. Nat Methods 13(2):127–137.  https://doi.org/10.1038/nmeth.3733 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR (2016) Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533(7603):420–424.  https://doi.org/10.1038/nature17946 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Nishida K, Arazoe T, Yachie N, Banno S, Kakimoto M, Tabata M, Mochizuki M, Miyabe A, Araki M, Hara KY, Shimatani Z, Kondo A (2016) Targeted nucleotide editing using hybrid prokaryotic and vertebrate adaptive immune systems. Science 353(6305):aaf8729.  https://doi.org/10.1126/science.aaf8729 CrossRefPubMedGoogle Scholar
  21. 21.
    Taglia A, Petillo R, D'Ambrosio P, Picillo E, Torella A, Orsini C, Ergoli M, Scutifero M, Passamano L, Palladino A, Nigro G, Politano L (2015) Clinical features of patients with dystrophinopathy sharing the 45-55 exon deletion of DMD gene. Acta Myol 34(1):9–13PubMedPubMedCentralGoogle Scholar
  22. 22.
    Ousterout DG, Kabadi AM, Thakore PI, Majoros WH, Reddy TE, Gersbach CA (2015) Multiplex CRISPR/Cas9-based genome editing for correction of dystrophin mutations that cause Duchenne muscular dystrophy. Nat Commun 6:6244.  https://doi.org/10.1038/ncomms7244 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Young CS, Hicks MR, Ermolova NV, Nakano H, Jan M, Younesi S, Karumbayaram S, Kumagai-Cresse C, Wang D, Zack JA, Kohn DB, Nakano A, Nelson SF, Miceli MC, Spencer MJ, Pyle AD (2016) A single CRISPR-Cas9 deletion strategy that targets the majority of DMD patients restores dystrophin function in hiPSC-derived muscle cells. Cell Stem Cell 18(4):533–540.  https://doi.org/10.1016/j.stem.2016.01.021 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Maggio I, Liu J, Janssen JM, Chen X, Goncalves MA (2016) Adenoviral vectors encoding CRISPR/Cas9 multiplexes rescue dystrophin synthesis in unselected populations of DMD muscle cells. Sci Rep 6:37051.  https://doi.org/10.1038/srep37051 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Beroud C, Collod-Beroud G, Boileau C, Soussi T, Junien C (2000) UMD (universal mutation database): a generic software to build and analyze locus-specific databases. Hum Mutat 15(1):86–94.  https://doi.org/10.1002/(SICI)1098-1004(200001)15:1<86::AID-HUMU16>3.0.CO;2-4 CrossRefPubMedGoogle Scholar
  26. 26.
    Aartsma-Rus A, Van Deutekom JCT, Fokkema IF, Van Ommen GJB, Den Dunnen JT (2006) Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule. Muscle Nerve 34(2):135–144.  https://doi.org/10.1002/mus.20586 CrossRefPubMedGoogle Scholar
  27. 27.
    White SJ, Aartsma-Rus A, Flanigan KM, Weiss RB, Kneppers AL, Lalic T, Janson AA, Ginjaar HB, Breuning MH, den Dunnen JT (2006) Duplications in the DMD gene. Hum Mutat 27(9):938–945.  https://doi.org/10.1002/humu.20367 CrossRefPubMedGoogle Scholar
  28. 28.
    Chapdelaine P, Pichavant C, Rousseau J, Paques F, Tremblay JP (2010) Meganucleases can restore the reading frame of a mutated dystrophin. Gene Ther 17(7):846–858.  https://doi.org/10.1038/gt.2010.26 CrossRefPubMedGoogle Scholar
  29. 29.
    Ousterout DG, Perez-Pinera P, Thakore PI, Kabadi AM, Brown MT, Qin X, Fedrigo O, Mouly V, Tremblay JP, Gersbach CA (2013) Reading frame correction by targeted genome editing restores dystrophin expression in cells from Duchenne muscular dystrophy patients. Mol Ther 21(9):1718–1726.  https://doi.org/10.1038/mt.2013.111 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Li HL, Fujimoto N, Sasakawa N, Shirai S, Ohkame T, Sakuma T, Tanaka M, Amano N, Watanabe A, Sakurai H, Yamamoto T, Yamanaka S, Hotta A (2015) Precise correction of the Dystrophin gene in Duchenne muscular dystrophy patient induced pluripotent stem cells by TALEN and CRISPR-Cas9. Stem Cell Rep 4(1):143–154.  https://doi.org/10.1016/j.stemcr.2014.10.013 CrossRefGoogle Scholar
  31. 31.
    Maggio I, Stefanucci L, Janssen JM, Liu J, Chen X, Mouly V, Goncalves MA (2016) Selection-free gene repair after adenoviral vector transduction of designer nucleases: rescue of dystrophin synthesis in DMD muscle cell populations. Nucleic Acids Res 44(3):1449–1470.  https://doi.org/10.1093/nar/gkv1540 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Ousterout DG, Kabadi AM, Thakore PI, Perez-Pinera P, Brown MT, Majoros WH, Reddy TE, Gersbach CA (2015) Correction of dystrophin expression in cells from duchenne muscular dystrophy patients through genomic excision of exon 51 by zinc finger nucleases. Mol Ther 23(3):523–532.  https://doi.org/10.1038/mt.2014.234 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Iyombe-Engembe JP, Ouellet DL, Barbeau X, Rousseau J, Chapdelaine P, Lague P, Tremblay JP (2016) Efficient restoration of the dystrophin gene reading frame and protein structure in DMD myoblasts using the CinDel method. Mol Ther Nucleic Acids 5:e283.  https://doi.org/10.1038/mtna.2015.58 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Nelson CE, Hakim CH, Ousterout DG, Thakore PI, Moreb EA, Castellanos Rivera RM, Madhavan S, Pan X, Ran FA, Yan WX, Asokan A, Zhang F, Duan D, Gersbach CA (2016) In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science 351(6271):403–407.  https://doi.org/10.1126/science.aad5143 CrossRefPubMedGoogle Scholar
  35. 35.
    Tabebordbar M, Zhu K, Cheng JK, Chew WL, Widrick JJ, Yan WX, Maesner C, Wu EY, Xiao R, Ran FA, Cong L, Zhang F, Vandenberghe LH, Church GM, Wagers AJ (2016) In vivo gene editing in dystrophic mouse muscle and muscle stem cells. Science 351(6271):407–411.  https://doi.org/10.1126/science.aad5177 CrossRefPubMedGoogle Scholar
  36. 36.
    Long C, Amoasii L, Mireault AA, McAnally JR, Li H, Sanchez-Ortiz E, Bhattacharyya S, Shelton JM, Bassel-Duby R, Olson EN (2016) Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science 351(6271):400–403.  https://doi.org/10.1126/science.aad5725 CrossRefPubMedGoogle Scholar
  37. 37.
    Bengtsson NE, Hall JK, Odom GL, Phelps MP, Andrus CR, Hawkins RD, Hauschka SD, Chamberlain JR, Chamberlain JS (2017) Muscle-specific CRISPR/Cas9 dystrophin gene editing ameliorates pathophysiology in a mouse model for Duchenne muscular dystrophy. Nat Commun 8:14454.  https://doi.org/10.1038/ncomms14454 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Xu L, Park KH, Zhao L, Xu J, El Refaey M, Gao Y, Zhu H, Ma J, Han R (2016) CRISPR-mediated genome editing restores dystrophin expression and function in mdx mice. Mol Ther 24(3):564–569.  https://doi.org/10.1038/mt.2015.192 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Popplewell L, Koo T, Leclerc X, Duclert A, Mamchaoui K, Gouble A, Mouly V, Voit T, Paques F, Cedrone F, Isman O, Yanez-Munoz RJ, Dickson G (2013) Gene correction of a duchenne muscular dystrophy mutation by meganuclease-enhanced exon knock-in. Hum Gene Ther 24(7):692–701.  https://doi.org/10.1089/hum.2013.081 CrossRefPubMedGoogle Scholar
  40. 40.
    Long CZ, McAnally JR, Shelton JM, Mireault AA, Bassel-Duby R, Olson EN (2014) Prevention of muscular dystrophy in mice by CRISPR/Cas9-mediated editing of germline DNA. Science 345(6201):1184–1188.  https://doi.org/10.1126/science.1254445 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Benabdallah BF, Duval A, Rousseau J, Chapdelaine P, Holmes MC, Haddad E, Tremblay JP, Beausejour CM (2013) Targeted gene addition of microdystrophin in mice skeletal muscle via human myoblast transplantation. Mol Ther Nucleic Acids 2:e68.  https://doi.org/10.1038/mtna.2012.55 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Filareto A, Parker S, Darabi R, Borges L, Iacovino M, Schaaf T, Mayerhofer T, Chamberlain JS, Ervasti JM, McIvor RS, Kyba M, Perlingeiro RCR (2013) An ex vivo gene therapy approach to treat muscular dystrophy using inducible pluripotent stem cells. Nat Commun 4:1549.  https://doi.org/10.1038/ncomms2550 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Wojtal D, Kemaladewi DU, Malam Z, Abdullah S, Wong TWY, Hyatt E, Baghestani Z, Pereira S, Stavropoulos J, Mouly V, Mamchaoui K, Muntoni F, Voit T, Gonorazky HD, Dowling JJ, Wilson MD, Mendoza-Londono R, Ivakine EA, Cohn RD (2016) Spell checking nature: versatility of CRISPR/Cas9 for developing treatments for inherited disorders. Am J Hum Genet 98(1):90–101.  https://doi.org/10.1016/j.ajhg.2015.11.012 CrossRefPubMedGoogle Scholar
  44. 44.
    Corbi N, Libri V, Fanciulli M, Tinsley JM, Davies KE, Passananti C (2000) The artificial zinc finger coding gene ‘Jazz’ binds the utrophin promoter and activates transcription. Gene Ther 7(12):1076–1083.  https://doi.org/10.1038/sj.gt.3301204 CrossRefPubMedGoogle Scholar
  45. 45.
    Strimpakos G, Corbi N, Pisani C, Di Certo MG, Onori A, Luvisetto S, Severini C, Gabanella F, Monaco L, Mattei E, Passananti C (2014) Novel adeno-associated viral vector delivering the utrophin gene regulator jazz counteracts dystrophic pathology in mdx mice. J Cell Physiol 229(9):1283–1291.  https://doi.org/10.1002/jcp.24567 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Perrin A, Rousseau J, Tremblay JP (2017) Increased expression of laminin subunit alpha 1 chain by dCas9-VP160. Mol Ther Nucleic Acids 6:68–79.  https://doi.org/10.1016/j.omtn.2016.11.004 CrossRefPubMedGoogle Scholar
  47. 47.
    Sibley CR, Blazquez L, Ule J (2016) Lessons from non-canonical splicing. Nat Rev Genet 17(7):407–421.  https://doi.org/10.1038/nrg.2016.46 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Zetsche B, Gootenberg JS, Abudayyeh OO, Slaymaker IM, Makarova KS, Essletzbichler P, Volz SE, Joung J, van der Oost J, Regev A, Koonin EV, Zhang F (2015) Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell 163(3):759–771.  https://doi.org/10.1016/j.cell.2015.09.038 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Wright AV, Nunez JK, Doudna JA (2016) Biology and applications of CRISPR systems: harnessing Nature’s toolbox for genome engineering. Cell 164(1–2):29–44.  https://doi.org/10.1016/j.cell.2015.12.035 CrossRefPubMedGoogle Scholar
  50. 50.
    Yin H, Xue W, Chen S, Bogorad RL, Benedetti E, Grompe M, Koteliansky V, Sharp PA, Jacks T, Anderson DG (2014) Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype. Nat Biotechnol 32(6):551–553.  https://doi.org/10.1038/nbt.2884 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Corti S, Nizzardo M, Simone C, Falcone M, Nardini M, Ronchi D, Donadoni C, Salani S, Riboldi G, Magri F, Menozzi G, Bonaglia C, Rizzo F, Bresolin N, Comi GP (2012) Genetic correction of human induced pluripotent stem cells from patients with spinal muscular atrophy. Sci Transl Med 4(165):165ra162.  https://doi.org/10.1126/scitranslmed.3004108 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Bahal R, Ali McNeer N, Quijano E, Liu Y, Sulkowski P, Turchick A, Lu YC, Bhunia DC, Manna A, Greiner DL, Brehm MA, Cheng CJ, Lopez-Giraldez F, Ricciardi A, Beloor J, Krause DS, Kumar P, Gallagher PG, Braddock DT, Mark Saltzman W, Ly DH, Glazer PM (2016) In vivo correction of anaemia in beta-thalassemic mice by gammaPNA-mediated gene editing with nanoparticle delivery. Nat Commun 7:13304.  https://doi.org/10.1038/ncomms13304 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Lattanzi A, Duguez S, Moiani A, Izmiryan A, Barbon E, Martin S, Mamchaoui K, Mouly V, Bernardi F, Mavilio F, Bovolenta M (2017) Correction of the exon 2 duplication in DMD myoblasts by a single CRISPR/Cas9 system. Mol Ther Nucleic Acids 7:11–19.  https://doi.org/10.1016/j.omtn.2017.02.004 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Maresca M, Lin VG, Guo N, Yang Y (2013) Obligate ligation-gated recombination (ObLiGaRe): custom-designed nuclease-mediated targeted integration through nonhomologous end joining. Genome Res 23(3):539–546.  https://doi.org/10.1101/gr.145441.112 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Auer TO, Duroure K, De Cian A, Concordet JP, Del Bene F (2014) Highly efficient CRISPR/Cas9-mediated knock-in in zebrafish by homology-independent DNA repair. Genome Res 24(1):142–153.  https://doi.org/10.1101/gr.161638.113 CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Suzuki K, Tsunekawa Y, Hernandez-Benitez R, Wu J, Zhu J, Kim EJ, Hatanaka F, Yamamoto M, Araoka T, Li Z, Kurita M, Hishida T, Li M, Aizawa E, Guo S, Chen S, Goebl A, Soligalla RD, Qu J, Jiang T, Fu X, Jafari M, Esteban CR, Berggren WT, Lajara J, Nunez-Delicado E, Guillen P, Campistol JM, Matsuzaki F, Liu GH, Magistretti P, Zhang K, Callaway EM, Zhang K, Belmonte JC (2016) In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration. Nature 540(7631):144–149.  https://doi.org/10.1038/nature20565 CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Nakade S, Tsubota T, Sakane Y, Kume S, Sakamoto N, Obara M, Daimon T, Sezutsu H, Yamamoto T, Sakuma T, Suzuki KT (2014) Microhomology-mediated end-joining-dependent integration of donor DNA in cells and animals using TALENs and CRISPR/Cas9. Nat Commun 5:5560.  https://doi.org/10.1038/ncomms6560 CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Perez-Pinera P, Ousterout DG, Brown MT, Gersbach CA (2012) Gene targeting to the ROSA26 locus directed by engineered zinc finger nucleases. Nucleic Acids Res 40(8):3741–3752.  https://doi.org/10.1093/nar/gkr1214 CrossRefPubMedGoogle Scholar
  59. 59.
    Hermann M, Maeder ML, Rector K, Ruiz J, Becher B, Burki K, Khayter C, Aguzzi A, Joung JK, Buch T, Pelczar P (2012) Evaluation of OPEN zinc finger nucleases for direct gene targeting of the ROSA26 locus in mouse embryos. PLoS One 7(9):e41796.  https://doi.org/10.1371/journal.pone.0041796 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Kasparek P, Krausova M, Haneckova R, Kriz V, Zbodakova O, Korinek V, Sedlacek R (2014) Efficient gene targeting of the Rosa26 locus in mouse zygotes using TALE nucleases. FEBS Lett 588(21):3982–3988.  https://doi.org/10.1016/j.febslet.2014.09.014 CrossRefPubMedGoogle Scholar
  61. 61.
    Remy S, Tesson L, Menoret S, Usal C, De Cian A, Thepenier V, Thinard R, Baron D, Charpentier M, Renaud JB, Buelow R, Cost GJ, Giovannangeli C, Fraichard A, Concordet JP, Anegon I (2014) Efficient gene targeting by homology-directed repair in rat zygotes using TALE nucleases. Genome Res 24(8):1371–1383.  https://doi.org/10.1101/gr.171538.113 CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Sato T, Sakuma T, Yokonishi T, Katagiri K, Kamimura S, Ogonuki N, Ogura A, Yamamoto T, Ogawa T (2015) Genome editing in mouse spermatogonial stem cell lines using TALEN and double-nicking CRISPR/Cas9. Stem Cell Rep 5(1):75–82.  https://doi.org/10.1016/j.stemcr.2015.05.011 CrossRefGoogle Scholar
  63. 63.
    Quadros RM, Harms DW, Ohtsuka M, Gurumurthy CB (2015) Insertion of sequences at the original provirus integration site of mouse ROSA26 locus using the CRISPR/Cas9 system. FEBS Open Bio 5:191–197.  https://doi.org/10.1016/j.fob.2015.03.003 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Nik-Ahd F, Bertoni C (2014) Ex vivo gene editing of the dystrophin gene in muscle stem cells mediated by peptide nucleic acid single stranded oligodeoxynucleotides induces stable expression of dystrophin in a mouse model for Duchenne muscular dystrophy. Stem Cells 32(7):1817–1830.  https://doi.org/10.1002/stem.1668 CrossRefPubMedGoogle Scholar
  65. 65.
    Cox DB, Platt RJ, Zhang F (2015) Therapeutic genome editing: prospects and challenges. Nat Med 21(2):121–131.  https://doi.org/10.1038/nm.3793 CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Yin H, Song CQ, Dorkin JR, Zhu LJ, Li Y, Wu Q, Park A, Yang J, Suresh S, Bizhanova A, Gupta A, Bolukbasi MF, Walsh S, Bogorad RL, Gao G, Weng Z, Dong Y, Koteliansky V, Wolfe SA, Langer R, Xue W, Anderson DG (2016) Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo. Nat Biotechnol 34(3):328–333.  https://doi.org/10.1038/nbt.3471 CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Gapinske M, Luu A, Winter J, Woods WS, Kostan KA, Shiva N, Song JS, Perez-Pinera P (2018) CRISPR-SKIP: programmable gene splicing with single base editors. Genome Biol 19:107CrossRefGoogle Scholar
  68. 68.
    Yuan J, Ma Y, Huang T, Chen Y, Peng Y, Li B, Li J, Zhang Y, Song B, Sun X, Ding Q, Song Y, Chang X (2018) Genetic modulation of RNA splicing with a CRISPR-guided cytidine deaminase. Mol Cell 72, 380–394Google Scholar
  69. 69.
    McGreevy JW, Hakim CH, McIntosh MA, Duan D (2015) Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy. Dis Model Mech 8(3):195–213.  https://doi.org/10.1242/dmm.018424 CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Bulfield G, Siller WG, Wight PA, Moore KJ (1984) X chromosome-linked muscular dystrophy (mdx) in the mouse. Proc Natl Acad Sci U S A 81(4):1189–1192CrossRefGoogle Scholar
  71. 71.
    Sicinski P, Geng Y, Ryder-Cook AS, Barnard EA, Darlison MG, Barnard PJ (1989) The molecular basis of muscular dystrophy in the mdx mouse: a point mutation. Science 244(4912):1578–1580CrossRefGoogle Scholar
  72. 72.
    Chandrasekharan K, Yoon JH, Xu Y, deVries S, Camboni M, Janssen PM, Varki A, Martin PT (2010) A human-specific deletion in mouse Cmah increases disease severity in the mdx model of Duchenne muscular dystrophy. Sci Transl Med 2(42):42ra54.  https://doi.org/10.1126/scitranslmed.3000692 CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    t Hoen PA, de Meijer EJ, Boer JM, Vossen RH, Turk R, Maatman RG, Davies KE, van Ommen GJ, van Deutekom JC, den Dunnen JT (2008) Generation and characterization of transgenic mice with the full-length human DMD gene. J Biol Chem 283(9):5899–5907.  https://doi.org/10.1074/jbc.M709410200 CrossRefGoogle Scholar
  74. 74.
    Robinson-Hamm JN, Nelson CE, Rivera RMC, Aartsma-Rus A, Asokan A, Gersbach CA (2016) 504. Restoration of Dystrophin expression by gene editing with S. aureus Cas9 in models of Duchenne muscular dystrophy. Mol Ther 24:S201.  https://doi.org/10.1016/S1525-0016(16)33313-5 CrossRefGoogle Scholar
  75. 75.
    Young CS, Mokhonova E, Quinonez M, Pyle AD, Spencer MJ (2017) Creation of a novel humanized dystrophic mouse model of duchenne muscular dystrophy and application of a CRISPR/Cas9 gene editing therapy. J Neuromuscul Dis 4(2):139–145CrossRefGoogle Scholar
  76. 76.
    Duan D (2015) Duchenne muscular dystrophy gene therapy in the canine model. Hum Gene Ther Clin Dev 26(1):57–69.  https://doi.org/10.1089/humc.2015.006 CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Amoasii L, Hildyard JCW, Li H, Sanchez-Ortiz E, Mireault A, Caballero D, Harron R, Stathopoulou TR, Massey C, Shelton JM, Bassel-Duby R, Piercy RJ, Olson EN (2018) Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy. Science 362(6410):86–91.  https://doi.org/10.1126/science.aau1549 CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Nakamura K, Fujii W, Tsuboi M, Tanihata J, Teramoto N, Takeuchi S, Naito K, Yamanouchi K, Nishihara M (2014) Generation of muscular dystrophy model rats with a CRISPR/Cas system. Sci Rep 4:5635.  https://doi.org/10.1038/srep05635 CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Yu HH, Zhao H, Qing YB, Pan WR, Jia BY, Zhao HY, Huang XX, Wei HJ (2016) Porcine zygote injection with Cas9/sgRNA results in DMD-modified pig with muscle dystrophy. Int J Mol Sci 17(10):1668.  https://doi.org/10.3390/ijms17101668 CrossRefPubMedCentralGoogle Scholar
  80. 80.
    Chen Y, Zheng Y, Kang Y, Yang W, Niu Y, Guo X, Tu Z, Si C, Wang H, Xing R, Pu X, Yang SH, Li S, Ji W, Li XJ (2015) Functional disruption of the dystrophin gene in rhesus monkey using CRISPR/Cas9. Hum Mol Genet 24(13):3764–3774.  https://doi.org/10.1093/hmg/ddv120 CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Nelson CE, Gersbach CA (2016) Engineering delivery vehicles for genome editing. Annu Rev Chem Biomol Eng 7:637–662CrossRefGoogle Scholar
  82. 82.
    Kotterman MA, Schaffer DV (2014) Engineering adeno-associated viruses for clinical gene therapy. Nat Rev Genet 15(7):445–451.  https://doi.org/10.1038/nrg3742 CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Sharma R, Anguela XM, Doyon Y, Wechsler T, DeKelver RC, Sproul S, Paschon DE, Miller JC, Davidson RJ, Shivak D, Zhou S, Rieders J, Gregory PD, Holmes MC, Rebar EJ, High KA (2015) In vivo genome editing of the albumin locus as a platform for protein replacement therapy. Blood 126(15):1777–1784.  https://doi.org/10.1182/blood-2014-12-615492 CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Chew WL, Tabebordbar M, Cheng JK, Mali P, Wu EY, Ng AH, Zhu K, Wagers AJ, Church GM (2016) A multifunctional AAV-CRISPR-Cas9 and its host response. Nat Methods 13(10):868–874.  https://doi.org/10.1038/nmeth.3993 CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Hendrickx R, Stichling N, Koelen J, Kuryk L, Lipiec A, Greber UF (2014) Innate immunity to adenovirus. Hum Gene Ther 25(4):265–284.  https://doi.org/10.1089/hum.2014.001 CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Wang D, Mou H, Li S, Li Y, Hough S, Tran K, Li J, Yin H, Anderson DG, Sontheimer E, Weng Z, Gao G, Xue W (2015) Adenovirus-mediated somatic genome editing of Pten by CRISPR/Cas9 in mouse liver in spite of Cas9-specific immune responses. Hum Gene Ther 26(7):432–442.  https://doi.org/10.1089/hum.2015.087 CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Hoggatt J (2016) Gene therapy for “bubble boy” disease. Cell 166(2):263.  https://doi.org/10.1016/j.cell.2016.06.049 CrossRefPubMedGoogle Scholar
  88. 88.
    Persons DA (2010) Lentiviral vector gene therapy: effective and safe? Mol Ther 18(5):861–862.  https://doi.org/10.1038/mt.2010.70 CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Nightingale SJ, Hollis RP, Pepper KA, Petersen D, Yu XJ, Yang C, Bahner I, Kohn DB (2006) Transient gene expression by nonintegrating lentiviral vectors. Mol Ther 13(6):1121–1132.  https://doi.org/10.1016/j.ymthe.2006.01.008 CrossRefPubMedGoogle Scholar
  90. 90.
    Lombardo A, Genovese P, Beausejour CM, Colleoni S, Lee YL, Kim KA, Ando D, Urnov FD, Galli C, Gregory PD, Holmes MC, Naldini L (2007) Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery. Nat Biotechnol 25(11):1298–1306.  https://doi.org/10.1038/nbt1353 CrossRefPubMedGoogle Scholar
  91. 91.
    Lee K, Conboy M, Park HM, Jiang F, Kim HJ, Dewitt MA, Mackley VA, Chang K, Rao A, Skinner C, Shobha T, Mehdipour M, Liu H, Huang WC, Lan F, Bray NL, Li S, Corn JE, Kataoka K, Doudna JA, Conboy I, Murthy N (2017) Nanoparticle delivery of Cas ribonucleoprotein and donor DNA in vivo induces homology-directed DNA repair. Nat Biomed Eng 1:889–901.  https://doi.org/10.1038/s41551-017-0137-2
  92. 92.
    Zuris JA, Thompson DB, Shu Y, Guilinger JP, Bessen JL, Hu JH, Maeder ML, Joung JK, Chen ZY, Liu DR (2015) Cationic lipid-mediated delivery of proteins enables efficient protein-based genome editing in vitro and in vivo. Nat Biotechnol 33(1):73–80.  https://doi.org/10.1038/nbt.3081 CrossRefPubMedGoogle Scholar
  93. 93.
    Darabi R, Arpke RW, Irion S, Dimos JT, Grskovic M, Kyba M, Perlingeiro RC (2012) Human ES- and iPS-derived myogenic progenitors restore DYSTROPHIN and improve contractility upon transplantation in dystrophic mice. Cell Stem Cell 10(5):610–619.  https://doi.org/10.1016/j.stem.2012.02.015 CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Maggio I, Chen XY, Goncalves MAFV (2016) The emerging role of viral vectors as vehicles for DMD gene editing. Genome Med 8:59.  https://doi.org/10.1186/s13073-016-0316-x CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Negroni E, Riederer I, Chaouch S, Belicchi M, Razini P, Di Santo J, Torrente Y, Butler-Browne GS, Mouly V (2009) In vivo myogenic potential of human CD133+ muscle-derived stem cells: a quantitative study. Mol Ther 17(10):1771–1778.  https://doi.org/10.1038/mt.2009.167 CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Benchaouir R, Meregalli M, Farini A, D'Antona G, Belicchi M, Goyenvalle A, Battistelli M, Bresolin N, Bottinelli R, Garcia L, Torrente Y (2007) Restoration of human dystrophin following transplantation of exon-skipping-engineered DMD patient stem cells into dystrophic mice. Cell Stem Cell 1(6):646–657.  https://doi.org/10.1016/j.stem.2007.09.016 CrossRefPubMedGoogle Scholar
  97. 97.
    Meng J, Chun S, Asfahani R, Lochmuller H, Muntoni F, Morgan J (2014) Human skeletal muscle-derived CD133+ cells form functional satellite cells after intramuscular transplantation in Immunodeficient host mice. Mol Ther 22(5):1008–1017.  https://doi.org/10.1038/mt.2014.26 CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Dellavalle A, Sampaolesi M, Tonlorenzi R, Tagliafico E, Sacchetti B, Perani L, Innocenzi A, Galvez BG, Messina G, Morosetti R, Li S, Belicchi M, Peretti G, Chamberlain JS, Wright WE, Torrente Y, Ferrari S, Bianco P, Cossu G (2007) Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nat Cell Biol 9(3):255–267.  https://doi.org/10.1038/ncb1542 CrossRefPubMedGoogle Scholar
  99. 99.
    Cossu G, Previtali SC, Napolitano S, Cicalese MP, Tedesco FS, Nicastro F, Noviello M, Roostalu U, Natali Sora MG, Scarlato M, De Pellegrin M, Godi C, Giuliani S, Ciotti F, Tonlorenzi R, Lorenzetti I, Rivellini C, Benedetti S, Gatti R, Marktel S, Mazzi B, Tettamanti A, Ragazzi M, Imro MA, Marano G, Ambrosi A, Fiori R, Sormani MP, Bonini C, Venturini M, Politi LS, Torrente Y, Ciceri F (2015) Intra-arterial transplantation of HLA-matched donor mesoangioblasts in Duchenne muscular dystrophy. EMBO Mol Med 7(12):1513–1528.  https://doi.org/10.15252/emmm.201505636 CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Torrente Y, Belicchi M, Sampaolesi M, Pisati F, Meregalli M, D'Antona G, Tonlorenzi R, Porretti L, Gavina M, Mamchaoui K, Pellegrino MA, Furling D, Mouly V, Butler-Browne GS, Bottinelli R, Cossu G, Bresolin N (2004) Human circulating AC133(+) stem cells restore dystrophin expression and ameliorate function in dystrophic skeletal muscle. J Clin Invest 114(2):182–195.  https://doi.org/10.1172/JCI20325 CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Kim S, Kim D, Cho SW, Kim J, Kim JS (2014) Highly efficient RNA-guided genome editing in human cells via delivery of purified Cas9 ribonucleoproteins. Genome Res 24(6):1012–1019.  https://doi.org/10.1101/gr.171322.113 CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Arnett ALH, Konieczny P, Ramos JN, Hall J, Odom G, Yablonka-Reuveni Z, Chamberlain JR (2014) Chamberlain JS (2014) Adeno-associated viral vectors do not efficiently target muscle satellite cells. Mol Ther Methods Clin Dev 1:14038.  https://doi.org/10.1038/mtm.2014.38 CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Hakim CH, Wasala NB, Nelson CE, Wasala LP, Yue Y, Louderman JA, Lessa TB, Dai A, Zhang K, Jenkins GJ, Nance ME, Pan X, Kodippili K, Yang NN, Chen SJ, Gersbach CA, Duan D (2018) AAV CRISPR editing rescues cardiac and muscle function for 18 months in dystrophic mice. JCI Insight 3(23):e124297CrossRefGoogle Scholar
  104. 104.
    Nelson CE, Wu Y, Gemberling MP, Oliver ML, Waller MA, Bohning JD, Robinson-Hamm JN, Bulaklak K, Castellanos Rivera RM, Collier JH, Asokan A, Gersbach CA (2019) Long-term evaluation of AAV-CRISPR genome editing for duchenne muscular dystrophy. Nat Med. In pressGoogle Scholar
  105. 105.
    Moore R, Spinhirne A, Lai MJ, Preisser S, Li Y, Kang T, Bleris L (2015) CRISPR-based self-cleaving mechanism for controllable gene delivery in human cells. Nucleic Acids Res 43(2):1297–1303.  https://doi.org/10.1093/nar/gku1326 CrossRefPubMedGoogle Scholar
  106. 106.
    Kosicki M, Tomberg K, Bradley A (2018) Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements. Nat Biotechnol 36:765–771CrossRefGoogle Scholar
  107. 107.
    Tsai SQ, Zheng Z, Nguyen NT, Liebers M, Topkar VV, Thapar V, Wyvekens N, Khayter C, Iafrate AJ, Le LP, Aryee MJ, Joung JK (2015) GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nat Biotechnol 33(2):187–197.  https://doi.org/10.1038/nbt.3117 CrossRefPubMedGoogle Scholar
  108. 108.
    Kim D, Kim S, Kim S, Park J, Kim JS (2016) Genome-wide target specificities of CRISPR-Cas9 nucleases revealed by multiplex Digenome-seq. Genome Res 26(3):406–415.  https://doi.org/10.1101/gr.199588.115 CrossRefPubMedPubMedCentralGoogle Scholar
  109. 109.
    Kleinstiver BP, Pattanayak V, Prew MS, Tsai SQ, Nguyen NT, Zheng Z, Joung JK (2016) High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature 529:490–495.  https://doi.org/10.1038/nature16526 CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Slaymaker IM, Gao L, Zetsche B, Scott DA, Yan WX, Zhang F (2016) Rationally engineered Cas9 nucleases with improved specificity. Science 351(6268):84–88.  https://doi.org/10.1126/science.aad5227 CrossRefPubMedGoogle Scholar
  111. 111.
    Kim D, Kim J, Hur JK, Been KW, Yoon SH, Kim JS (2016) Genome-wide analysis reveals specificities of Cpf1 endonucleases in human cells. Nat Biotechnol 34(8):863–868.  https://doi.org/10.1038/nbt.3609 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Christopher E. Nelson
    • 1
    • 2
  • Charles A. Gersbach
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Biomedical EngineeringDuke UniversityDurhamUSA
  2. 2.Center for Genomic and Computational BiologyDuke UniversityDurhamUSA
  3. 3.Department of Orthopaedic SurgeryDuke University Medical CenterDurhamUSA

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