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Genome Editing in Therapy of Genodermatoses

  • MAMMALIAN GENOME EDITING
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Abstract

This review is devoted to the prospects for the use of fundamentally important approaches and methods for the correction and therapy of genodermatoses, a group of inherited skin diseases. The greatest number of methods was applicable for the group of inherited epidermolysis bullosa. Gene replacement using viral and non-viral methods of delivery to cells has been replaced by genome editing using programmable nucleases used both in vitro and in vivo. The focus is on more widely used methods applied in vitro to various cell types. The description of the methods used is classified based on the use of DNA break repair pathways: the canonical non-homologous end-reconnection pathway—cNHEJ, and directed homologous recombination—HDR. The choice of editing strategy depends on the type of mutation causing the disease, the type of mutation inheritance, and the nucleotide environment of the mutation. Animal disease models obtained by genome editing are considered. The experience of developing methods for editing the genome and their application for the treatment of genodermatoses, previously recognized as incurable, is summarized.

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REFERENCES

  1. Naso G., Petrova A. 2020. Cellular therapy options for genetic skin disorders with a focus on recessive dystrophic epidermolysis bullosa. Br. Med. Bull. 136, 30–45.

    Article  Google Scholar 

  2. Kueckelhaus M., Rothoeft T., De Rosa L., Yeni B., Ohmann T., Maier C., Eitner L., Metze D., Losi L., Secone Seconetti A., De Luca M., Hirsch T. 2021. Transgenic epidermal cultures for junctional epidermolysis bullosa—5-year outcomes. N. Eng. J. Med. 385, 2264–2270.

    Article  Google Scholar 

  3. Dinnes J., Deeks J.J., Chuchu N., Matin R.N., Wong K.Y., Aldridge R.B., Durack A., Gulati A., Chan S.A., Johnston L., Bayliss S.E., Leonardi-Bee J., Takwoingi Y., Davenport C., O’Sullivan C., Tehrani H., Williams H.C. 2018. Visual inspection and dermoscopy, alone or in combination, for diagnosing keratinocyte skin cancers in adults. Cochrane Database Systematic Rev. 2018, CD011901.

    Google Scholar 

  4. Dourado Alcorte M., Sogayar M.C., Demasi M.A. 2019. Patent landscape of molecular and cellular targeted therapies for recessive dystrophic epidermolysis bullosa. Exper. Opin. Ther. Patents. 29, 327–337.

    Article  CAS  Google Scholar 

  5. Lwin S.M., Syed F., Di W.-L., Kadiyirire T., Liu L., Guy A., Petrova A., Abdul-Wahab A., Reid F., Phillips R., Elstad M., Georgiadis C., Aristodemou S., Lovell P.A., McMillan J.R., Mee J., Miskinyte S., Titeux M., Ozoemena L., Pramanik R., Serrano S., Rowles R., Maurin C., Orrin E., Martinez-Queipo M., Rashidghamat E., Tziotzios C., Onoufriadis A., Chen M., Chan L., Farzaneh F., Del Rio M., Tolar J., Bauer J.W., Larcher F., Antoniou M.N., Hovnanian A., Thra-sher A.J., Mellerio J.E., Qasim W., McGrath J.A. 2019. Safety and early efficacy outcomes for lentiviral fibroblast gene therapy in recessive dystrophic epidermolysis bullosa. JCI Insight. 4, 126243.

    Article  Google Scholar 

  6. Siprashvili Z., Nguyen N.T., Gorell E.S., Loutit K., Khuu P., Furukawa L.K., Lorenz H.P., Leung T.H., Keene D.R., Rieger K.E., Khavari P., Lane A.T., Tang J.Y., Marinkovich M.P. 2016. Safety and wound outcomes following genetically corrected autologous epidermal grafts in patients with recessive dystrophic epidermolysis bullosa. J. Am. Med. Assoc. 316, 1808–1817.

    Article  Google Scholar 

  7. Kubanov A.A., Chikin V.V., Karamova A.E., Monchakovskaya E.S. 2021. Topical treatment of inherited epidermolysis bullosa. Vestn. Dermatol. Venerol. 97, 6–19.

    Google Scholar 

  8. Bardhan A., Bruckner-Tuderman L., Chapple I.L.C., Fine J.-D., Harper N., Has C., Magin T.M., Marinkovich M.P., Marshall J.F., McGrath J.A., Mellerio J.E., Polson R., Heagerty A.H. 2020. Epidermolysis bullosa. Nat. Rev. Dis. Primers. 6, 78.

    Article  Google Scholar 

  9. Yang W.S., Kang S., Sung J., Kleinman H.K. 2019. Thymosin β4: potential to treat epidermolysis bullosa and other severe dermal injuries. Eur. J. Dermatol. 29, 459–467.

    Article  CAS  Google Scholar 

  10. Feramisco J.D., Sadreyev R.I., Murray M.L., Grishin N.V., Tsao H. 2009. Phenotypic and genotypic analyses of genetic skin disease through the online Mendelian inheritance in man (OMIM) Database. J. Invest. Dermatol. 129, 2628–2636.

    Article  CAS  Google Scholar 

  11. Rao R., Mellerio J., Bhogal B.S., Groves R. 2012. Immunofluorescence antigen mapping for hereditary epidermolysis bullosa. Indian J. Dermatol., Venereol. Leprol. 78, 692–697.

    Article  Google Scholar 

  12. Yenamandra V.K., Bhari N., Ray S.B., Sreenivas V., Dinda A.K., Scaria V., Sharma V.K., Sethuraman G. 2017. Diagnosis of inherited epidermolysis bullosa in resource-limited settings: immunohistochemistry revisited. Dermatology (Basel). 233, 326–332.

    Article  CAS  Google Scholar 

  13. Ohashi M., Shu E., Nagai M., Murase K., Nakano H., Tamai K., Sawamura D., Hiroka T., Seishima M., Kitajima Y., Aoyama Y. 2011. Two cases of recessive dystrophic epidermolysis bullosa diagnosed as severe generalized. J. Dermatol. 38, 893–899.

    CAS  Google Scholar 

  14. Rossi S., Castiglia D., Pisaneschi E., Diociaiuti A., Stracuzzi A., Cesario C., Mariani R., Floriddia G., Zambruno G., Boldrini R., Abeni D., Novelli A., Alaggio R., El Hachem M. 2021. Immunofluorescence mapping, electron microscopy and genetics in the diagnosis and sub-classification of inherited epidermolysis bullosa: a single-centre retrospective comparative study of 87 cases with long-term follow-up. J. Eur. Acad. Dermatol. Venereol. 35, 1007–1016.

    Article  CAS  Google Scholar 

  15. Krylova Y., Drobintseva A., Polyakova V., Kvetnoy I., Panteleev L., Musikhin S., Barzda V. 2015. Nonlinear optical microscopy as applied to biomedical investigations. Biotekhnosfera. 2–7.

  16. Anker P., Fésűs L., Kiss N., Noll J., Becker K., Kuroli E., Mayer B., Bozsányi S., Lőrincz K., Lihacova I., Lihachev A., Lange M., Wikonkál N., Medvecz M. 2021. Visualization of keratin with diffuse reflectance and autofluorescence imaging and nonlinear optical microscopy in a rare keratinopathic ichthyosis. Sensors (Basel). 21, 1105.

    Article  CAS  Google Scholar 

  17. Has C., Bruckner-Tuderman L. 2014. The genetics of skin fragility. Annu. Rev. Genomics Hum. Genet. 15, 245–268.

    Article  CAS  Google Scholar 

  18. Coulombe P.A., Lee C.-H. 2012. Defining keratin protein function in skin epithelia: epidermolysis bullosa simplex and its aftermath. J. Invest. Dermatol. 132, 763–775.

    Article  CAS  Google Scholar 

  19. Goldberg I., Fruchter D., Meilick A., Schwartz M.E., Sprecher E. 2014. Best treatment practices for Pachyonychia congenita. J. Eur. Acad. Dermatol. Venereol. 28, 279–285.

    Article  CAS  Google Scholar 

  20. Smith F.J., Hansen C.D., Hull P.R., Kaspar R.L., McLean W.I., O′Toole E., Sprecher E. 2006. Pachyonychia congenita. In GeneReviews®. Adam M.P., Ardinger H.H., Pagon R.A., Wallace S.E., Bean L.J., Gripp K.W., Mirzaa G.M., Amemiya A., Eds. Seattle (WA): Univ. Washington, Seattle.

  21. van den Akker P.C., van Essen A.J., Kraak M.M.J., Meijer R., Nijenhuis M., Meijer G., Hofstra R.M.W., Pas H.H., Scheffer H., Jonkman M.F. 2009. Long-term follow-up of patients with recessive dystrophic epidermolysis bullosa in the Netherlands: expansion of the mutation database and unusual phenotype-genotype correlations. J. Dermatol. Sci. 56, 9–18.

    Article  CAS  Google Scholar 

  22. Dang N., Murrell D.F. 2008. Mutation analysis and characterization of COL7A1 mutations in dystrophic epidermolysis bullosa. Exp. Dermatol. 17, 553–568.

    Article  CAS  Google Scholar 

  23. Dang N., Klingberg S., Marr P., Murrell D.F. 2007. Review of collagen VII sequence variants found in Australasian patients with dystrophic epidermolysis bullosa reveals nine novel COL7A1 variants. J. Dermatol. Sci. 46, 169–178.

    Article  CAS  Google Scholar 

  24. Freiberg R.A., Choate K.A., Deng H., Alperin E.S., Shapiro L.J., Khavari P.A. 1997. A model of corrective gene transfer in X-linked ichthyosis. Hum. Mol. Genet. 6, 927–933.

    Article  CAS  Google Scholar 

  25. March O.P., Lettner T., Klausegger A., Ablinger M., Kocher T., Hainzl S., Peking P., Lackner N., Rajan N., Hofbauer J.P., Guttmann-Gruber C., Bygum A., Koller U., Reichelt J. 2019. Gene editing-mediated disruption of epidermolytic ichthyosis-associated KRT10 alleles restores filament stability in keratinocytes. J. Invest. Dermatol. 139, 1699–1710. e6.

    Article  CAS  Google Scholar 

  26. Magnaldo T., Sarasin A. 2004. Xeroderma pigmentosum: from symptoms and genetics to gene-based skin therapy. Cells Tissues Organs. 177, 189–198.

    Article  Google Scholar 

  27. Warrick E., Garcia M., Chagnoleau C., Chevallier O., Bergoglio V., Sartori D., Mavilio F., Angulo J.F., Avril M.-F., Sarasin A., Larcher F., Del Rio M., Bernerd F., Magnaldo T. 2012. Preclinical corrective gene transfer in xeroderma pigmentosum human skin stem cells. Mol. Ther. 20, 798–807.

    Article  CAS  Google Scholar 

  28. Dang L., Zhou X., Zhong X., Yu W., Huang S., Liu H., Chen Y., Zhang W., Yuan L., Li L., Huang X., Li G., Liu J., Tong G. 2022. Correction of the pathogenic mutation in TGM1 gene by adenine base editing in mutant embryos. Mol. Ther. 30, 175–183.

    Article  CAS  Google Scholar 

  29. Gálvez V., Chacón-Solano E., Bonafont J., Mencía Á., Di W.-L., Murillas R., Llames S., Vicente A., Del Rio M., Carretero M., Larcher F. 2020. Efficient CRISPR-Cas9-mediated gene ablation in human keratinocytes to recapitulate genodermatoses: modeling of Netherton syndrome. Mol. Ther.—Methods Clin. Dev. 18, 280–290.

    Article  Google Scholar 

  30. Petek L.M., Fleckman P., Miller D.G. 2010. Efficient KRT14 targeting and functional characterization of transplanted human keratinocytes for the treatment of epidermolysis bullosa simplex. Mol. Ther. 18, 1624–1632.

    Article  CAS  Google Scholar 

  31. Aushev M., Koller U., Mussolino C., Cathomen T., Reichelt J. 2017. Traceless targeting and isolation of gene-edited immortalized keratinocytes from epidermolysis bullosa simplex patients. Mol. Ther.—Methods Clin. Dev. 6, 112–123.

    Article  CAS  Google Scholar 

  32. Kocher T., Peking P., Klausegger A., Murauer E.M., Hofbauer J.P., Wally V., Lettner T., Hainzl S., Ablinger M., Bauer J.W., Reichelt J., Koller U. 2017. Cut and paste: efficient homology-directed repair of a dominant negative KRT14 mutation via CRISPR/Cas9 nickases. Mol. Ther. 25, 2585–2598.

    Article  CAS  Google Scholar 

  33. Hirsch T., Rothoeft T., Teig N., Bauer J.W., Pellegrini G., De Rosa L., Scaglione D., Reichelt J., Klausegger A., Kneisz D., Romano O., Secone Seconetti A., Contin R., Enzo E., Jurman I., Carulli S., Jacobsen F., Luecke T., Lehnhardt M., Fischer M., Kueckelhaus M., Quaglino D., Morgante M., Bicciato S., Bondanza S., De Luca M. 2017. Regeneration of the entire human epidermis using transgenic stem cells. Nature. 551, 327–332.

    Article  CAS  Google Scholar 

  34. Sebastiano V., Zhen H.H., Haddad B., Derafshi B.H., Bashkirova E., Melo S.P., Wang P., Leung T.L., Siprashvili Z., Tichy A., Li J., Ameen M., Hawkins J., Lee S., Li L., Schwertschkow A., Bauer G., Lisowski L., Kay M.A., Kim S.K., Lane A.T., Wernig M., Oro A.E. 2014. Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa. Sci. Translat. Med. 6, 264ra163.

  35. van den Akker P.C., Mellerio J.E., Martinez A.E., Liu L., Meijer R., Dopping-Hepenstal P.J.C., van Essen A.J., Scheffer H., Hofstra R.M.W., McGrath J.A., Jonkman M.F. 2011. The inversa type of recessive dystrophic epidermolysis bullosa is caused by specific arginine and glycine substitutions in type VII collagen. J. Med. Genet. 48, 160–167.

    Article  CAS  Google Scholar 

  36. Nickless A., Bailis J.M., You Z. 2017. Control of gene expression through the nonsense-mediated RNA decay pathway. Cell Biosci. 7, 26.

    Article  Google Scholar 

  37. Supek F., Lehner B., Lindeboom R.G.H. 2021. To NMD or not to NMD: nonsense-mediated mrna decay in cancer and other genetic diseases. Trends Genet. 37, 657–668.

    Article  CAS  Google Scholar 

  38. Khajavi M., Inoue K., Lupski J.R. 2006. Nonsense-mediated mRNA decay modulates clinical outcome of genetic disease. Eur. J. Hum. Genet. 14, 1074–1081.

    Article  CAS  Google Scholar 

  39. March O.P., Kocher T., Koller U. 2020. Context-dependent strategies for enhanced genome editing of genodermatoses. Cells. 9 (1), 112. https://doi.org/10.3390/cells9010112

    Article  CAS  Google Scholar 

  40. Mecklenbeck S., Compton S.H., Mejía J.E., Cervini R., Hovnanian A., Bruckner-Tuderman L., Barrandon Y. 2002. A microinjected COL7A1-PAC vector restores synthesis of intact procollagen VII in a dystrophic epidermolysis bullosa keratinocyte cell line. Hum. Gene Ther. 13, 1655–1662.

    Article  CAS  Google Scholar 

  41. Sat E., Leung K.H., Bruckner-Tuderman L., Cheah K.S. 2000. Tissue-specific expression and long-term deposition of human collagen VII in the skin of transgenic mice: implications for gene therapy. Gene Ther. 7, 1631–1639.

    Article  CAS  Google Scholar 

  42. Di W.-L., Larcher F., Semenova E., Talbot G.E., Harper J.I., Del Rio M., Thrasher A.J., Qasim W. 2011. Ex-vivo gene therapy restores LEKTI activity and corrects the architecture of Netherton syndrome-derived skin grafts. Mol. Ther. 19, 408–416.

    Article  CAS  Google Scholar 

  43. Lwin S.M., Syed F., Di W.L., Kadiyirire T., Liu L., Guy A., Petrova A., Abdul-Wahab A., Reid F., Phillips R., Elstad M., Georgiadis C., Aristodemou., Lovell P.A., McMillan J.R., Mee J., Miskinyte S., Titeux M., Ozoemena L., Pramanik R., Serrano S., Rowles R., Maurin C., Orrin E., Martinez-Queipo M., Rashidghamat E., Tziotzios C., Onoufriadis A., Chen M., Chan L., Farzaneh F., Del Rio M., Tolar J., Bauer J.W., Larcher F., Antoniou M.N., Hovnanian A., Thrasher A.J., Mellerio J.E., Qasim W., McGrath J.A. 2019. Safety and early efficacy outcomes for lentiviral fibroblast gene therapy in recessive dystrophic epidermolysis bullosa. JCI Insight. 4 (11), e126243. https://doi.org/10.1172/jci.insight.126243

    Article  Google Scholar 

  44. Georgiadis C., Syed F., Petrova A., Abdul-Wahab A., Lwin S.M., Farzaneh F., Chan L., Ghani S., Fleck R.A., Glover L., McMillan J.R., Chen M., Thrasher A.J., McGrath J.A., Di W.-L., Qasim W. 2016. Lentiviral engineered fibroblasts expressing codon-optimized COL7A1 restore anchoring fibrils in RDEB. J. Invest. Dermatol. 136, 284–292.

    Article  CAS  Google Scholar 

  45. Mavilio F., Pellegrini G., Ferrari S., Di Nunzio F., Di Iorio E., Recchia A., Maruggi G., Ferrari G., Provasi E., Bonini C., Capurro S., Conti A., Magnoni C., Giannetti A., De Luca M. 2006. Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat. Med. 12, 1397–1402.

    Article  CAS  Google Scholar 

  46. elo S.P., Lisowski L., Bashkirova E., Zhen H.H., Chu K., Keene D.R., Marinkovich M.P., Kay M.A., Oro A.E. 2014. Somatic correction of junctional epidermolysis bullosa by a highly recombinogenic AAV variant. Mol. Ther. 22, 725–733

    Article  CAS  Google Scholar 

  47. Roedl D., Oji V., Buters J.T.M., Behrendt H., Braun-Falco M. 2011. rAAV2-mediated restoration of LEKTI in LEKTI-deficient cells from Netherton patients. J. Dermatol. Sci. 61, 194–198.

    Article  CAS  Google Scholar 

  48. South A.P., Uitto J. 2016. Type VII collagen replacement therapy in recessive dystrophic epidermolysis bullosa-how much, how often? J. Invest. Dermatol. 136, 1079–1081.

    Article  CAS  Google Scholar 

  49. Eichstadt S., Barriga M., Ponakala A., Teng C., Nguyen N.T., Siprashvili Z., Nazaroff J., Gorell E.S., Chiou A.S., Taylor L., Khuu P., Keene D.R., Rieger K., Khosla R.K., Furukawa L.K., Lorenz H.P., Marinkovich M.P., Tang J.Y. 2019. Phase 1/2a clinical trial of gene-corrected autologous cell therapy for recessive dystrophic epidermolysis bullosa. JCI Insight. 4, 130554.

    Article  Google Scholar 

  50. Woodley D.T., Krueger G.G., Jorgensen C.M., Fairley J.A., Atha T., Huang Y., Chan L., Keene D.R., Chen M. 2003. Normal and gene-corrected dystrophic epidermolysis bullosa fibroblasts alone can produce type VII collagen at the basement membrane zone. J. Invest. Dermatol. 121, 1021–1028.

    Article  CAS  Google Scholar 

  51. Wu W., Lu Z., Li F., Wang W., Qian N., Duan J., Zhang Y., Wang F., Chen T. 2017. Efficient in vivo gene editing using ribonucleoproteins in skin stem cells of recessive dystrophic epidermolysis bullosa mouse model. Proc. Natl. Acad. Sci. U. S. A. 114, 1660–1665.

    Article  CAS  Google Scholar 

  52. Gurevich I., Agarwal P., Zhang P., Dolorito J.A., Oliver S., Liu H., Reitze N., Sarma N., Bagci I.S., Sridhar K., Kakarla V., Yenamandra V.K., O’Malley M., Prisco M., Tufa S.F., Keene D.R., South A.P., Krishnan S.M., Marinkovich M.P. 2022. In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Nat. Med. 28 (4), 780–789

    Article  CAS  Google Scholar 

  53. Pasmooij A.M.G., Pas H.H., Bolling M.C., Jonkman M.F. 2007. Revertant mosaicism in junctional epidermolysis bullosa due to multiple correcting second-site mutations in LAMB3. J. Clin. Invest. 117, 1240–1248.

    Article  CAS  Google Scholar 

  54. Umegaki-Arao N., Pasmooij A.M.G., Itoh M., Cerise J.E., Guo Z., Levy B., Gostyński A., Rothman L.R., Jonkman M.F., Christiano A.M. 2014. Induced pluripotent stem cells from human revertant keratinocytes for the treatment of epidermolysis bullosa. Sci. Translat. Med. 6, 264ra164.

  55. Jonkman M.F., Pasmooij A.M.G. 2009. Revertant mosaicism—patchwork in the skin. N. Eng. J. Med. 360, 1680–1682.

    Article  CAS  Google Scholar 

  56. Twaroski K., Eide C., Riddle M.J., Xia L., Lees C.J., Chen W., Mathews W., Keene D.R., McGrath J.A., Tolar J. 2019. Revertant mosaic fibroblasts in recessive dystrophic epidermolysis bullosa. Br. J. Dermatol. 181, 1247–1253.

    Article  CAS  Google Scholar 

  57. Tolar J., McGrath J.A., Xia L., Riddle M.J., Lees C.J., Eide C., Keene D.R., Liu L., Osborn M.J., Lund T.C., Blazar B.R., Wagner J.E. 2014. Patient-specific naturally gene-reverted induced pluripotent stem cells in recessive dystrophic epidermolysis bullosa. J. Invest. Dermatol. 134, 1246–1254.

    Article  CAS  Google Scholar 

  58. Sasaki M., Abe R., Fujita Y., Ando S., Inokuma D., Shimizu H. 2008. Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type. J. Immunol. 180, 2581–2587.

    Article  CAS  Google Scholar 

  59. Geyer M.B., Radhakrishnan K., Giller R., Umegaki N., Harel S., Kiuru M., Morel K.D., LeBoeuf N., Kandel J., Bruckner A., Fabricatore S., Chen M., Woodley D., McGrath J., Baxter-Lowe L., Uitto J., Christiano A.M., Cairo M.S. 2015. Reduced toxicity conditioning and allogeneic hematopoietic progenitor cell transplantation for recessive dystrophic epidermolysis bullosa. J. Pediatrics. 167, 765–769. e1.

  60. Fujita Y., Komatsu M., Lee S.E., Kushida Y., Nakayama-Nishimura C., Matsumura W., Takashima S., Shinkuma S., Nomura T., Masutomi N., Kawamura M., Dezawa M., Shimizu H. 2021. Intravenous injection of muse cells as a potential therapeutic approach for epidermolysis bullosa. J. Invest. Dermatol. 141, 198–202. e6.

  61. Rashidghamat E., Kadiyirire T., Ayis S., Petrof G., Liu L., Pullabhatla V., Ainali C., Guy A., Aristodemou S., McMillan J.R., Ozoemena L., Mee J., Pramanik R., Saxena A., Nuamah R., de Rinaldis E., Serrano S., Maurin C., Martinez-Queipo M., Lwin S.M., Ilic D., Martinez A., Dazzi F., Slaper-Cortenbach I., Wes-tinga K., Zeddies S., van den Broek M., Onoufriadis A., Mellerio J.E., McGrath J.A. 2020. Phase I/II open-label trial of intravenous allogeneic mesenchymal stromal cell therapy in adults with recessive dystrophic epidermolysis bullosa. J. Am. Acad. Dermatol. 83, 447–454.

    Article  CAS  Google Scholar 

  62. Masonic Cancer Center, University of Minnesota 2022. MT2015-20: biochemical correction of severe epidermolysis bullosa by allogeneic cell transplantation and serial donor mesenchymal cell infusions. Clin. Trial Reg. clinicaltrials.gov.

  63. Ebens C.L., McGrath J.A., Tamai K., Hovnanian A., Wagner J.E., Riddle M.J., Keene D.R., DeFor T.E., Tryon R., Chen M., Woodley D.T., Hook K., Tolar J. 2019. Bone marrow transplant with post-transplant cyclophosphamide for recessive dystrophic epidermolysis bullosa expands the related donor pool and permits tolerance of nonhaematopoietic cellular grafts. Br. J. Dermatol. 181, 1238–1246.

    Article  CAS  Google Scholar 

  64. Itoh M., Kawagoe S., Tamai K., Nakagawa H., Asahina A., Okano H.J. 2020. Footprint-free gene mutation correction in induced pluripotent stem cell (iPSC) derived from recessive dystrophic epidermolysis bullosa (RDEB) using the CRISPR/Cas9 and piggyBac transposon system. J. Dermatol. Sci. 98, 163–172.

    Article  CAS  Google Scholar 

  65. Ruiz-Torres S., Lambert P.F., Wikenheiser-Brokamp K.A., Wells S.I. 2021. Directed differentiation of human pluripotent stem cells into epidermal stem and progenitor cells. Mol. Biol. Rep. 48, 6213–6222.

    Article  CAS  Google Scholar 

  66. Wenzel D., Bayerl J., Nyström A., Bruckner-Tuderman L., Meixner A., Penninger J.M. 2014. Genetically corrected iPSCs as cell therapy for recessive dystrophic epidermolysis bullosa. Sci. Translat. Med. 6, 264ra165.

  67. Itoh M., Kiuru M., Cairo M.S., Christiano A.M. 2011. Generation of keratinocytes from normal and recessive dystrophic epidermolysis bullosa-induced pluripotent stem cells. Proc. Natl. Acad. Sci. U. S. A. 108, 8797–8802.

    Article  CAS  Google Scholar 

  68. Blackford A.N., Jackson S.P. 2017. ATM, ATR, and DNA-PK: the trinity at the heart of the DNA damage response. Mol. Cell. 66, 801–817.

    Article  CAS  Google Scholar 

  69. Kantidze O.L., Velichko A.K., Luzhin A.V., Petrova N.V., Razin S.V. 2018. Synthetically lethal interactions of ATM, ATR, and DNA-PKcs. Trends Cancer. 4, 755–768.

    Article  CAS  Google Scholar 

  70. Goodarzi A.A., Yu Y., Riballo E., Douglas P., Wal-ker S.A., Ye R., Härer C., Marchetti C., Morrice N., Jeggo P.A., Lees-Miller S.P. 2006. DNA-PK autophosphorylation facilitates Artemis endonuclease activity. EMBO J. 25, 3880–3889.

    Article  CAS  Google Scholar 

  71. Her J., Bunting S.F. 2018. How cells ensure correct repair of DNA double-strand breaks. J. Biol. Chem. 293, 10502–10511.

    Article  CAS  Google Scholar 

  72. Mao Z., Bozzella M., Seluanov A., Gorbunova V. 2008. Comparison of nonhomologous end joining and homologous recombination in human cells. DNA Repair. 7, 1765–1771.

    Article  CAS  Google Scholar 

  73. Symington L.S. 2016. Mechanism and regulation of DNA end resection in eukaryotes. Crit. Rev. Biochem. Mol. Biol. 51, 195–212.

    Article  CAS  Google Scholar 

  74. Shamanna R.A., Lu H., de Freitas J.K., Tian J., Croteau D.L., Bohr V.A. 2016. WRN regulates pathway choice between classical and alternative non-homologous end joining. Nat. Commun. 7, 13785.

    Article  Google Scholar 

  75. Jayavaradhan R., Pillis D.M., Goodman M., Zhang F., Zhang Y., Andreassen P.R., Malik P. 2019. CRISPR-Cas9 fusion to dominant-negative 53BP1 enhances HDR and inhibits NHEJ specifically at Cas9 target sites. Nat. Commun. 10, 2866.

    Article  Google Scholar 

  76. Osborn M.J., Starker C.G., McElroy A.N., Webber B.R., Riddle M.J., Xia L., DeFeo A.P., Gabriel R., Schmidt M., Von Kalle C., Carlson D.F., Maeder M.L., Joung J.K., Wagner J.E., Voytas D.F., Blazar B.R., Tolar J. 2013. TALEN-based gene correction for epidermolysis bullosa. Mol. Therapy. 21, 1151–1159.

    Article  CAS  Google Scholar 

  77. Jiang F., Zhou K., Ma L., Gressel S., Doudna J.A. 2015. Structural biology. A Cas9-guide RNA complex preorganized for target DNA recognition. Science (New York, N.Y.). 348, 1477–1481.

    Article  CAS  Google Scholar 

  78. Slaymaker I.M., Gao L., Zetsche B., Scott D.A., Yan W.X., Zhang F. 2016. Rationally engineered Cas9 nucleases with improved specificity. Science. 351, 84–88.

    Article  CAS  Google Scholar 

  79. Kim D.Y., Lee J.M., Moon S.B., Chin H.J., Park S., Lim Y., Kim D., Koo T., Ko J.-H., Kim Y.-S. 2022. Efficient CRISPR editing with a hypercompact Cas12f1 and engineered guide RNAs delivered by adeno-associated virus. Nat. Biotechnol. 40, 94–102.

    Article  CAS  Google Scholar 

  80. Yang H., Ren S., Yu S., Pan H., Li T., Ge S., Zhang J., Xia N. 2020. Methods favoring homology-directed repair choice in response to CRISPR/Cas9 induced-double strand breaks. Int. J. Mol. Sci. 21, E6461.

    Article  Google Scholar 

  81. Shinkuma S., Guo Z., Christiano A.M. 2016. Site-specific genome editing for correction of induced pluripotent stem cells derived from dominant dystrophic epidermolysis bullosa. Proc. Natl. Acad. Sci. U. S. A. 113, 5676–5681.

    Article  CAS  Google Scholar 

  82. Kocher T., Koller U. 2021. Chapter three—advances in gene editing strategies for epidermolysis bullosa. Prog. Mol. Biol. Transl. Sci. 182, 81–109.

    Article  CAS  Google Scholar 

  83. Gretzmeier C., Pin D., Kern J.S., Chen M., Woodley D.T., Bruckner-Tuderman L., de Souza M.P., Nyström A. 2022. Systemic collagen VII replacement therapy for advanced recessive dystrophic epidermolysis bullosa. J. Invest. Dermatol. 142 (4), 1094‒1102.e3.

    Article  CAS  Google Scholar 

  84. Zauner R., Wimmer M., Dorfer S., Ablinger M., Koller U., Piñón Hofbauer J., Guttmann-Gruber C., Bauer J.W., Wally V. 2022. Transcriptome-guided drug repurposing for aggressive SCCs. Internat. J. Mol. Sci. 23, 1007.

    Article  CAS  Google Scholar 

  85. Vanden Oever M., Muldoon D., Mathews W., Tolar J. 2021. Fludarabine modulates expression of type VII collagen during haematopoietic stem cell transplantation for recessive dystrophic epidermolysis bullosa. Br. J. Dermatol. 185, 380–390.

    Article  CAS  Google Scholar 

  86. Chamorro C., Mencía A., Almarza D., Duarte B., Büning H., Sallach J., Hausser I., Del Río M., Larcher F., Murillas R. 2016. Gene editing for the efficient correction of a recurrent COL7A1 mutation in recessive dystrophic epidermolysis bullosa keratinocytes. Mol. Ther.—Nucleic Acids. 5, e307.

    Article  CAS  Google Scholar 

  87. Mencía Á., Chamorro C., Bonafont J., Duarte B., Holguin A., Illera N., Llames S.G., Escámez M.J., Hausser I., Del Río M., Larcher F., Murillas R. 2018. Deletion of a pathogenic mutation-containing exon of COL7A1 allows clonal gene editing correction of RDEB patient epidermal stem cells. Mol. Ther.—Nucleic Acids. 11, 68–78.

    Article  Google Scholar 

  88. Bonafont J., Mencía Á., García M., Torres R., Rodríguez S., Carretero M., Chacón-Solano E., Modamio-Høybjør S., Marinas L., León C., Escamez M.J., Hausser I., Del Río M., Murillas R., Larcher F. 2019. Clinically relevant correction of recessive dystrophic epidermolysis bullosa by dual sgRNA CRISPR/Cas9-mediated gene editing. Mol. Ther. 27, 986–998.

    Article  CAS  Google Scholar 

  89. Sawamura D., Goto M., Yasukawa K., Sato-Matsumura K., Nakamura H., Ito K., Nakamura H., Tomita Y., Shimizu H. 2005. Genetic studies of 20 Japanese families of dystrophic epidermolysis bullosa. J. Hum. Genet. 50, 543–546.

    Article  Google Scholar 

  90. Takashima S., Shinkuma S., Fujita Y., Nomura T., Ujiie H., Natsuga K., Iwata H., Nakamura H., Vorobyev A., Abe R., Shimizu H. 2019. Efficient gene reframing therapy for recessive dystrophic epidermolysis bullosa with CRISPR/Cas9. J. Invest. Dermatol. 139, 1711–1721. e4.

  91. Jacków J., Guo Z., Hansen C., Abaci H.E., Doucet Y.S., Shin J.U., Hayashi R., DeLorenzo D., Kabata Y., Shinkuma S., Salas-Alanis J.C., Christiano A.M. 2019. CRISPR/Cas9-based targeted genome editing for correction of recessive dystrophic epidermolysis bullosa using iPS cells. Proc. Natl. Acad. Sci. U. S. A. 116, 26846–26852.

    Article  Google Scholar 

  92. Artegiani B., Hendriks D., Beumer J., Kok R., Zheng X., Joore I., Chuva de Sousa Lopes S., van Zon J., Tans S., Clevers H. 2020. Fast and efficient generation of knock-in human organoids using homology-independent CRISPR-Cas9 precision genome editing. Nat. Cell Biol. 22, 321–331.

    Article  CAS  Google Scholar 

  93. Eki R., She J., Parlak M., Benamar M., Du K.-P., Kumar P., Abbas T. 2020. A robust CRISPR-Cas9-based fluorescent reporter assay for the detection and quantification of DNA double-strand break repair. Nucleic Acids Res. 48, e126.

    Article  CAS  Google Scholar 

  94. Izmiryan A., Ganier C., Bovolenta M., Schmitt A., Mavilio F., Hovnanian A. 2018. Ex vivo COL7A1 correction for recessive dystrophic epidermolysis bullosa using CRISPR/Cas9 and homology-directed repair. Mol. Ther.—Nucleic Acids. 12, 554–567.

    Article  Google Scholar 

  95. Kocher T., Bischof J., Haas S.A., March O.P., Liemberger B., Hainzl S., Illmer J., Hoog A., Muigg K., Binder H.-M., Klausegger A., Strunk D., Bauer J.W., Cathomen T., Koller U. 2021. A non-viral and selection-free COL7A1 HDR approach with improved safety profile for dystrophic epidermolysis bullosa. Mol. Ther.—Nucleic Acids. 25, 237–250.

    Article  CAS  Google Scholar 

  96. Osborn M.J., Lees C.J., McElroy A.N., Merkel S.C., Eide C.R., Mathews W., Feser C.J., Tschann M., McElmury R.T., Webber B.R., Kim C.J., Blazar B.R., Tolar J. 2018. CRISPR/Cas9-based cellular engineering for targeted gene overexpression. Int. J. Mol. Sci. 19, E946.

    Article  Google Scholar 

  97. Benati D., Miselli F., Cocchiarella F., Patrizi C., Carretero M., Baldassarri S., Ammendola V., Has C., Colloca S., Rio M.D., Larcher F., Recchia A. 2018. CRISPR/Cas9-mediated in situ correction of LAMB3 gene in keratinocytes derived from a junctional epidermolysis bullosa patient. Mol. Ther. 26, 2592–2603.

    Article  CAS  Google Scholar 

  98. Bornert O., Kühl T., Bremer J., van den Akker P.C., Pasmooij A.M., Nyström A. 2016. Analysis of the functional consequences of targeted exon deletion in COL7A1 reveals prospects for dystrophic epidermolysis bullosa therapy. Mol. Ther. 24, 1302–1311.

    Article  CAS  Google Scholar 

  99. Koga H., Hamada T., Ishii N., Fukuda S., Sakaguchi S., Nakano H., Tamai K., Sawamura D., Hashimoto T. 2011. Exon 87 skipping of the COL7A1 gene in dominant dystrophic epidermolysis bullosa. J. Dermatol. 38, 489–492.

    Article  CAS  Google Scholar 

  100. McGrath J.A., Ashton G.H., Mellerio J.E., Salas-Alanis J.C., Swensson O., McMillan J.R., Eady R.A. 1999. Moderation of phenotypic severity in dystrophic and junctional forms of epidermolysis bullosa through in-frame skipping of exons containing non-sense or frameshift mutations J. Invest. Dermatol. 113, 314–321.

    Article  CAS  Google Scholar 

  101. Saito M., Masunaga T., Ishiko A. 2009. A novel de novo splice-site mutation in the COL7A1 gene in dominant dystrophic epidermolysis bullosa (DDEB): specific exon skipping could be a prognostic factor for DDEB pruriginosa. Clin. Exp. Dermatol. 34, e934–936.

    Article  CAS  Google Scholar 

  102. Bremer J., van der Heijden E.H., Eichhorn D.S., Meijer R., Lemmink H.H., Scheffer H., Sinke R.J., Jonkman M.F., Pasmooij A.M.G., Van den Akker P.C. 2019. Natural exon skipping sets the stage for exon skipping as therapy for dystrophic epidermolysis bullosa. Mol. Ther.—Nucleic Acids. 18, 465–475.

    Article  CAS  Google Scholar 

  103. Lim K.R.Q., Yoon C., Yokota T. 2018. Applications of CRISPR/Cas9 for the treatment of Duchenne muscular dystrophy. J. Pers. Med. 8, 38.

    Article  Google Scholar 

  104. Vermeer F.C., Bremer J., Sietsma R.J., Sandilands A., Hickerson R.P., Bolling M.C., Pasmooij A.M.G., Lemmink H.H., Swertz M.A., Knoers N.V.A.M., van der Velde K.J., van den Akker P.C. 2021. Therapeutic prospects of exon skipping for epidermolysis bullosa. Int. J. Mol. Sci. 22, 12222.

    Article  CAS  Google Scholar 

  105. Ran F.A., Hsu P.D., Lin C.-Y., Gootenberg J.S., Konermann S., Trevino A.E., Scott D.A., Inoue A., Matoba S., Zhang Y., Zhang F. 2013. Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell. 154, 1380–1389.

    Article  CAS  Google Scholar 

  106. Kocher T., Wagner R.N., Klausegger A., Guttmann-Gruber C., Hainzl S., Bauer J.W., Reichelt J., Koller U. 2019. Improved double-nicking strategies for COL7A1-editing by homologous recombination. Mol. Ther.–Nucleic Acids. 18, 496–507.

    Article  CAS  Google Scholar 

  107. Paquet D., Kwart D., Chen A., Sproul A., Jacob S., Teo S., Olsen K.M., Gregg A., Noggle S., Tessier-Lavigne M. 2016. Efficient introduction of specific homozygous and heterozygous mutations using CRISPR/Cas9. Nature. 533, 125–129.

    Article  CAS  Google Scholar 

  108. Zhang X., Jin H., Huang X., Chaurasiya B., Dong D., Shanley T.P., Zhao Y.-Y. 2022. Robust genome editing in adult vascular endothelium by nanoparticle delivery of CRISPR-Cas9 plasmid DNA. Cell Rep. 38, 110196.

    Article  CAS  Google Scholar 

  109. Huang T.P., Newby G.A., Liu D.R. 2021. Precision genome editing using cytosine and adenine base editors in mammalian cells. Nat. Protoc. 16, 1089–1128.

    Article  CAS  Google Scholar 

  110. Gaudelli N.M., Komor A.C., Rees H.A., Packer M.S., Badran A.H., Bryson D.I., Liu D.R. 2017. Programmable base editing of A⋅T to G⋅C in genomic DNA without DNA cleavage. Nature. 551, 464–471.

    Article  CAS  Google Scholar 

  111. Rees H.A., Komor A.C., Yeh W.-H., Caetano-Lopes J., Warman M., Edge A.S.B., Liu D.R. 2017. Improving the DNA specificity and applicability of base editing through protein engineering and protein delivery. Nat. Commun. 8, 15790.

    Article  CAS  Google Scholar 

  112. Osborn M.J., Newby G.A., McElroy A.N., Knipping F., Nielsen S.C., Riddle M.J., Xia L., Chen W., Eide C.R., Webber B.R., Wandall H.H., Dabelsteen S., Blazar B.R., Liu D.R., Tolar J. 2020. Base editor correction of COL7A1 in recessive dystrophic epidermolysis bullosa patient-derived fibroblasts and iPSCs. J. Invest. Dermatol. 140, 338–347. e5.

  113. Doman J.L., Raguram A., Newby G.A., Liu D.R. 2020. Evaluation and minimization of Cas9-independent off-target DNA editing by cytosine base editors. Nat. Biotechnol. 38, 620–628.

    Article  CAS  Google Scholar 

  114. Bowden A.R., Morales-Juarez D.A., Sczaniecka-Clift M., Agudo M.M., Lukashchuk N., Thomas J.C., Jackson S.P. 2020. Parallel CRISPR-Cas9 screens clarify impacts of p53 on screen performance. eLife. 9, e55325.

    Article  Google Scholar 

  115. Fu X., Wu S., Li B., Xu Y., Liu J. 2020. Functions of p53 in pluripotent stem cells. Protein Cell. 11, 71–78.

    Article  CAS  Google Scholar 

  116. Ihry R.J., Worringer K.A., Salick M.R., Frias E., Ho D., Theriault K., Kommineni S., Chen J., Sondey M., Ye C., Randhawa R., Kulkarni T., Yang Z., McAllister G., Russ C., Reece-Hoyes J., Forrester W., Hoffman G.R., Dolmetsch R., Kaykas A. 2018. p53 inhibits CRISPR-Cas9 engineering in human pluripotent stem cells. Nat. Med. 24, 939–946.

    Article  CAS  Google Scholar 

  117. Allen F., Crepaldi L., Alsinet C., Strong A.J., Kleshchevnikov V., De Angeli P., Páleníková P., Khodak A., Kiselev V., Kosicki M., Bassett A.R., Harding H., Galanty Y., Muñoz-Martínez F., Metzakopian E., Jackson S.P., Parts L. 2019. Predicting the mutations generated by repair of Cas9-induced double-strand breaks. Nat. Biotechnol. 37, 64–72.

    Article  CAS  Google Scholar 

  118. Chakrabarti A.M., Henser-Brownhill T., Monserrat J., Poetsch A.R., Luscombe N.M., Scaffidi P. 2019. Target-specific precision of CRISPR-mediated genome editing. Mol. Cell. 73, 699–713. e6.

  119. Shen M.W., Arbab M., Hsu J.Y., Worstell D., Culbertson S.J., Krabbe O., Cassa C.A., Liu D.R., Gifford D.K., Sherwood R.I. 2018. Predictable and precise template-free CRISPR editing of pathogenic variants. Nature. 563, 646–651.

    Article  CAS  Google Scholar 

  120. Bae S., Kweon J., Kim H.S., Kim J.-S. 2014. Microhomology-based choice of Cas9 nuclease target sites. Nat. Methods. 11, 705–706.

    Article  CAS  Google Scholar 

  121. Tatiossian K.J., Clark R.D.E., Huang C., Thornton M.E., Grubbs B.H., Cannon P.M. 2021. Rational selection of CRISPR-Cas9 guide RNAs for homology-directed genome editing. Mol. Ther. 29, 1057–1069.

    Article  CAS  Google Scholar 

  122. Kim S.-I., Matsumoto T., Kagawa H., Nakamura M., Hirohata R., Ueno A., Ohishi M., Sakuma T., Soga T., Yamamoto T., Woltjen K. 2018. Microhomology-assisted scarless genome editing in human iPSCs. Nat. Commun. 9, 939.

    Article  Google Scholar 

  123. Anzalone A.V., Randolph P.B., Davis J.R., Sousa A.A., Koblan L.W., Levy J.M., Chen P.J., Wilson C., Newby G.A., Raguram A., Liu D.R. 2019. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature. 576, 149–157.

    Article  CAS  Google Scholar 

  124. Hsu J.Y., Grünewald J., Szalay R., Shih J., Anzalone A.V., Lam K.C., Shen M.W., Petri K., Liu D.R., Joung J.K., Pinello L. 2021. PrimeDesign software for rapid and simplified design of prime editing guide RNAs. Nat. Commun. 12, 1034.

    Article  CAS  Google Scholar 

  125. Renz P., Imahorn E., Spoerri I., Aushev M., March O.P., Wariwoda H., Von Arb S., Volz A., Itin P.H., Reichelt J., Burger B. 2019. Arginine- but not alanine-rich carboxy-termini trigger nuclear translocation of mutant keratin 10 in ichthyosis with confetti. J. Cell. Mol. Med. 23, 8442–8452.

    Article  CAS  Google Scholar 

  126. Garcia T.M., Kiener S., Jagannathan V., Russell D.S., Leeb T. 2020. A COL7A1 variant in a litter of neonatal Basset Hounds with dystrophic epidermolysis bullosa. Genes. 11, E1458.

    Article  Google Scholar 

  127. Niskanen J., Dillard K., Arumilli M., Salmela E., Anttila M., Lohi H., Hytönen M.K. 2017. Nonsense variant in COL7A1 causes recessive dystrophic epidermolysis bullosa in Central Asian Shepherd dogs. PLoS One. 12, e0177527.

    Article  Google Scholar 

  128. Pausch H., Ammermüller S., Wurmser C., Hamann H., Tetens J., Drögemüller C., Fries R. 2016. A nonsense mutation in the COL7A1 gene causes epidermolysis bullosa in Vorderwald cattle. BMC Genet. 17, 149.

    Article  Google Scholar 

  129. Ding B., Ryder O.A., Wang X., Bai S.C., Zhou S.Q., Zhang Y. 2000. Molecular basis of albinism in the rhesus monkey. Mutat. Res. 449, 1–6.

    Article  CAS  Google Scholar 

  130. Johnson A.L., Peterson S.M., Terry M.ML., Ferguson B., Colgin L.M., Lewis A.D. 2020. Spontaneous KRT5 gene mutation in rhesus macaques (Macaca mulatta): a novel nonhuman primate model of epidermolysis bullosa simplex. Vet. Pathol. 57, 344–348.

    Article  CAS  Google Scholar 

  131. Heinonen S., Männikkö M., Klement J.F., Whitaker-Menezes D., Murphy G.F., Uitto J. 1999. Targeted inactivation of the type VII collagen gene (Col7A1) in mice results in severe blistering phenotype: a model for recessive dystrophic epidermolysis bullosa. J. Cell Sci. 112 (Pt 21), 3641–3648.

    Article  CAS  Google Scholar 

  132. Fritsch A., Loeckermann S., Kern J.S., Braun A., Bösl M.R., Bley T.A., Schumann H., von Elverfeldt D., Paul D., Erlacher M., Berens von Rautenfeld D., Hausser I., Fässler R., Bruckner-Tuderman L. 2008. A hypomorphic mouse model of dystrophic epidermolysis bullosa reveals mechanisms of disease and response to fibroblast therapy. J. Clin. Invest. 118, 1669–1679.

    Article  CAS  Google Scholar 

  133. Kühl T., Mezger M., Hausser I., Guey L.T., Handgretinger R., Bruckner-Tuderman L., Nyström A. 2016. Collagen VII half-life at the dermal-epidermal junction zone: implications for mechanisms and therapy of genodermatoses. J. Invest. Dermatol. 136, 1116–1123.

    Article  Google Scholar 

  134. Hou Y., Guey L.T., Wu T., Gao R., Cogan J., Wang X., Hong E., Vivian Ning W., Keene D., Liu N., Huang Y., Kaftan C., Tangarone B., Quinones-Garcia I., Uitto J., Francone O.L., Woodley D.T., Chen M. 2015. Intravenously administered recombinant human type VII collagen derived from chinese hamster ovary cells reverses the disease phenotype in recessive dystrophic epidermolysis bullosa mice. J. Invest. Dermatol. 135, 3060–3067.

    Article  CAS  Google Scholar 

  135. Nyström A., Velati D., Mittapalli V.R., Fritsch A., Kern J.S., Bruckner-Tuderman L. 2013. Collagen VII plays a dual role in wound healing. J. Clin. Invest. 123, 3498–3509.

    Article  Google Scholar 

  136. Nishie W., Sawamura D., Goto M., Ito K., Shibaki A., McMillan J.R., Sakai K., Nakamura H., Olasz E., Yancey K.B., Akiyama M., Shimizu H. 2007. Humanization of autoantigen. Nat. Med. 13, 378–383.

    Article  CAS  Google Scholar 

  137. Luan X.-R., Chen X.-L., Tang Y.-X., Zhang J.-Y., Gao X., Ke H.-P., Lin Z.-Y., Zhang X.-N. 2018. CRISPR/Cas9-mediated treatment ameliorates the phenotype of epidermolytic palmoplantar keratoderma-like mouse. Mol. Ther.–Nucleic Acids. 12, 220–228.

    Article  Google Scholar 

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Funding

The work was supported by the Russian Foundation for Basic Research (project no. 19-29-04044) and Ivanenko was supported by the Ministry of Science and Higher Education (project no. 075-15-2019-1789)

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  1. Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, 1177997, Moscow, Russia

    A. V. Ivanenko, N. A. Evtushenko & N. G. Gurskaya

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  1. A. V. Ivanenko
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  2. N. A. Evtushenko
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Translated by N. Onishchenko

Abbreviation: EB, epidermolysis bullosa; EB, inherited epidermolysis bullosa; DEB, dystrophic epidermolysis bullosa; EBS, epidermolysis bullosa simplex; DDEB, dominant dystrophic epidermolysis bullosa; RDEB, recessive dystrophic epidermolysis bullosa; JEB, junctional epidermolysis bullosa; KRT, keratin genes; COL7A1, type VII collagen α-1 chain gene; C7, collagen α chain; DSB, double-stranded break; HR, homologous recombination; HDR, homology directed repair; c-NHEJ, canonical non-homologous end joining; iPSC, induced pluripotent stem cells.

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Ivanenko, A.V., Evtushenko, N.A. & Gurskaya, N.G. Genome Editing in Therapy of Genodermatoses. Mol Biol 56, 921–941 (2022). https://doi.org/10.1134/S0026893322060085

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