Leading edge: emerging drug, cell, and gene therapies for junctional epidermolysis bullosa

References

• Fine JD. Epidemiology of inherited epidermolysis bullosa based on incidence and prevalence estimates from the national epidermolysis bullosa registry. JAMA Dermatol. 2016 Nov 1;152(11):1231–1238.
   PubMed Web of Science ®Google Scholar
• Meneguzzi G, Marinkovich MP, Aberdam D, et al. Kalinin is abnormally expressed in epithelial basement membranes of Herlitz’s junctional epidermolysis bullosa patients. Exp Dermatol. 1992 Dec;1(5):221–229.
   PubMedGoogle Scholar
• Jonkman MF, de Jong MC, Heeres K, et al. 180-kD bullous pemphigoid antigen (BP180) is deficient in generalized atrophic benign epidermolysis bullosa. J Clin Invest. 1995 Mar;95(3):1345–1352.
   PubMed Web of Science ®Google Scholar
• Brown TA, Gil SG, Sybert VP, et al. Defective integrin alpha 6 beta 4 expression in the skin of patients with junctional epidermolysis bullosa and pyloric atresia. J Invest Dermatol. 1996 Sep;107(3):384–391.
   PubMed Web of Science ®Google Scholar
• Ko L, Griggs CL, Mylonas KS, et al. A nonlethal case of junctional epidermolysis bullosa and congenital pyloric atresia: compound heterozygosity in a patient with a novel integrin beta 4 gene mutation. J Pediatr. 2018;193:261–264 e1.
   PubMed Web of Science ®Google Scholar
• Junctional Epidermolysis Bullosa. [Internet]. Seattle (WA): University of Washington. 2018; [cited 2019 Dec 1]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1125/.
   Google Scholar
• Hammersen J, Has C, Naumann-Bartsch N, et al. Genotype, clinical course, and therapeutic decision making in 76 infants with severe generalized junctional epidermolysis bullosa. J Invest Dermatol. 2016 Nov;136(11):2150–2157.
   PubMed Web of Science ®Google Scholar
• Yan EG, Paris JJ, Ahluwalia J, et al. Treatment decision-making for patients with the Herlitz subtype of junctional epidermolysis bullosa. J Perinatol. 2007 May;27(5):307–311.
   PubMed Web of Science ®Google Scholar
• Denyer J, Pillay E, Clapham J. Best practice guidelines for skin and wound care in epidermolysis bullosa: an international consensus. Wounds International; London, UK. 2017.
   Google Scholar
• Mavilio F, Pellegrini G, Ferrari S, et al. Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat Med. 2006 Dec;12(12):1397–1402.
   PubMed Web of Science ®Google Scholar
• Hirsch T, Rothoeft T, Teig N, et al. Regeneration of the entire human epidermis using transgenic stem cells. Nature. 2017 Nov 16;551(7680):327–332.
   PubMed Web of Science ®Google Scholar
• Bauer JW, Koller J, Murauer EM, et al. Closure of a large chronic wound through transplantation of gene-corrected epidermal stem cells. J Invest Dermatol. 2017 Mar;137(3):778–781.
   PubMed Web of Science ®Google Scholar
• Gurtner GC, Werner S, Barrandon Y, et al. Wound repair and regeneration. Nature. 2008 May 15;453(7193):314–321.
   PubMed Web of Science ®Google Scholar
• Engelhardt E, Toksoy A, Goebeler M, et al. Chemokines IL-8, GROalpha, MCP-1, IP-10, and Mig are sequentially and differentially expressed during phase-specific infiltration of leukocyte subsets in human wound healing. Am J Pathol. 1998 Dec;153(6):1849–1860.
   PubMed Web of Science ®Google Scholar
• Ridiandries A, Tan JTM, Bursill CA. The role of chemokines in wound healing. Int J Mol Sci. 2018 Oct 18;19(10). DOI:10.3390/ijms19103217.
   PubMed Web of Science ®Google Scholar
• Dekoninck S, Blanpain C. Stem cell dynamics, migration and plasticity during wound healing. Nat Cell Biol. 2019 Jan;21(1):18–24.
   PubMed Web of Science ®Google Scholar
• Iorio V, Troughton LD, Hamill KJ. Laminins: roles and utility in wound repair. Adv Wound Care. 2015 Apr 1;4(4):250–263.
   Web of Science ®Google Scholar
• Wilgus TA, Roy S, McDaniel JC. Neutrophils and wound repair: positive actions and negative reactions. Adv Wound Care . 2013 Sep;2(7):379–388.
   PubMedGoogle Scholar
• Walko G, Castanon MJ, Wiche G. Molecular architecture and function of the hemidesmosome. Cell Tissue Res. 2015 Jun;360(3):529–544.
   PubMed Web of Science ®Google Scholar
• Nishie W, Kiritsi D, Nystrom A, et al. Dynamic interactions of epidermal collagen XVII with the extracellular matrix: laminin 332 as a major binding partner. Am J Pathol. 2011 Aug;179(2):829–837.
   PubMed Web of Science ®Google Scholar
• Bhattacharjee O, Ayyangar U, Kurbet AS, et al. Unraveling the ECM-immune cell crosstalk in skin diseases. Front Cell Dev Biol. 2019;7:68.
   PubMed Web of Science ®Google Scholar
• Vivinus-Nebot M, Ticchioni M, Mary F, et al. Laminin 5 in the human thymus: control of T cell proliferation via alpha6beta4 integrins. J Cell Biol. 1999 Feb 8;144(3):563–574.
   PubMed Web of Science ®Google Scholar
• Sime W, Lunderius-Andersson C, Enoksson M, et al. Human mast cells adhere to and migrate on epithelial and vascular basement membrane laminins LM-332 and LM-511 via alpha3beta1 integrin. J Immunol. 2009 Oct 1;183(7):4657–4665.
   PubMed Web of Science ®Google Scholar
• Simon T, Bromberg JS. Regulation of the immune system by laminins. Trends Immunol. 2017 Nov;38(11):858–871.
   PubMed Web of Science ®Google Scholar
• Ebeling S, Naumann K, Pollok S, et al. From a traditional medicinal plant to a rational drug: understanding the clinically proven wound healing efficacy of birch bark extract. PLoS One. 2014;9(1):e86147.
   PubMed Web of Science ®Google Scholar
• Behm B, Babilas P, Landthaler M, et al. Cytokines, chemokines and growth factors in wound healing. J Eur Acad Dermatol Venereol. 2012 Jul;26(7):812–820.
   PubMed Web of Science ®Google Scholar
• Barrientos S, Stojadinovic O, Golinko MS, et al. Growth factors and cytokines in wound healing. Wound Repair Regen. 2008 Sep-Oct;16(5):585–601.
   PubMed Web of Science ®Google Scholar
• Kern JS, Schwieger-Briel A, Lowe S, et al. Oleogel-S10 Phase 3 study “EASE” for epidermolysis bullosa: study design and rationale. Trials. 2019 Jun 11;20(1):350.
   PubMedGoogle Scholar
• Frew Q, Rennekampff HO, Dziewulski P, et al. Betulin wound gel accelerated healing of superficial partial thickness burns: results of a randomized, intra-individually controlled, phase III trial with 12-months follow-up. Burns. 2019 Jun;45(4):876–890.
   PubMed Web of Science ®Google Scholar
• Barret JP, Podmelle F, Lipovy B, et al. Accelerated re-epithelialization of partial-thickness skin wounds by a topical betulin gel: results of a randomized phase III clinical trials program. Burns. 2017 Sep;43(6):1284–1294.
   PubMed Web of Science ®Google Scholar
• Schwieger-Briel A, Kiritsi D, Schempp C, et al. Betulin-based oleogel to improve wound healing in dystrophic epidermolysis bullosa: a prospective controlled proof-of-concept study. Dermatol Res Pract. 2017;2017:5068969.
   PubMed Web of Science ®Google Scholar
• Alexeev V, Salas-Alanis JC, Palisson F, et al. Pro-inflammatory chemokines and cytokines dominate the blister fluid molecular signature in patients with epidermolysis bullosa and affect leukocyte and stem cell migration. J Invest Dermatol. 2017 Nov;137(11):2298–2308.
   PubMed Web of Science ®Google Scholar
• Kleinman HK, Sosne G. Thymosin beta4 promotes dermal healing. Vitam Horm. 2016;102:251–275.
   PubMed Web of Science ®Google Scholar
• Huff T, Muller CS, Otto AM, et al. Beta-thymosins, small acidic peptides with multiple functions. Int J Biochem Cell Biol. 2001 Mar;33(3):205–220.
   PubMed Web of Science ®Google Scholar
• Young JD, Lawrence AJ, MacLean AG, et al. Thymosin beta 4 sulfoxide is an anti-inflammatory agent generated by monocytes in the presence of glucocorticoids. Nat Med. 1999 Dec;5(12):1424–1427.
   PubMed Web of Science ®Google Scholar
• Malinda KM, Sidhu GS, Mani H, et al. Thymosin beta 4 accelerates wound healing. J Invest Dermatol. 1999 Sep;113(3):364–368.
   PubMed Web of Science ®Google Scholar
• Sosne G, Chan CC, Thai K, et al. Thymosin beta 4 promotes corneal wound healing and modulates inflammatory mediators in vivo. Exp Eye Res. 2001 May;72(5):605–608.
   PubMed Web of Science ®Google Scholar
• Philp D, Badamchian M, Scheremeta B, et al. Thymosin beta 4 and a synthetic peptide containing its actin-binding domain promote dermal wound repair in db/db diabetic mice and in aged mice. Wound Repair Regen. 2003 Jan-Feb;11(1):19–24.
   PubMed Web of Science ®Google Scholar
• Sosne G, Xu L, Prach L, et al. Thymosin beta 4 stimulates laminin-5 production independent of TGF-beta. Exp Cell Res. 2004 Feb 1;293(1):175–183.
   PubMed Web of Science ®Google Scholar
• Treadwell T, Kleinman HK, Crockford D, et al. The regenerative peptide thymosin beta4 accelerates the rate of dermal healing in preclinical animal models and in patients. Ann N Y Acad Sci. 2012 Oct;1270(1):37–44.
   PubMedGoogle Scholar
• Friesen WJ, Johnson B, Sierra J, et al. The minor gentamicin complex component, X2, is a potent premature stop codon readthrough molecule with therapeutic potential. PLoS One. 2018;13(10):e0206158.
   PubMed Web of Science ®Google Scholar
• Woodley DT, Cogan J, Hou Y, et al. Gentamicin induces functional type VII collagen in recessive dystrophic epidermolysis bullosa patients. J Clin Invest. 2017 Aug 1;127(8):3028–3038.
   PubMed Web of Science ®Google Scholar
• Lincoln V, Cogan J, Hou Y, et al. Gentamicin induces LAMB3 nonsense mutation readthrough and restores functional laminin 332 in junctional epidermolysis bullosa. Proc Natl Acad Sci U S A. 2018 Jul 10;115(28):E6536–E6545.
   PubMed Web of Science ®Google Scholar
• Garreau de Loubresse N, Prokhorova I, Holtkamp W, et al. Structural basis for the inhibition of the eukaryotic ribosome. Nature. 2014 Sep 25;513(7519):517–522.
   PubMed Web of Science ®Google Scholar
• Floquet C, Hatin I, Rousset JP, et al. Statistical analysis of readthrough levels for nonsense mutations in mammalian cells reveals a major determinant of response to gentamicin. PLoS Genet. 2012;8(3):e1002608.
   PubMed Web of Science ®Google Scholar
• Varki R, Sadowski S, Pfendner E, et al. Epidermolysis bullosa. I. Molecular genetics of the junctional and hemidesmosomal variants. J Med Genet. 2006 Aug;43(8):641–652.
   PubMed Web of Science ®Google Scholar
• Carter DM, Lin AN, Varghese MC, et al. Treatment of junctional epidermolysis bullosa with epidermal autografts. J Am Acad Dermatol. 1987 Aug;17(2):246–250.
   PubMed Web of Science ®Google Scholar
• Yuen WY, Huizinga J, Jonkman MF. Punch grafting of chronic ulcers in patients with laminin-332-deficient, non-Herlitz junctional epidermolysis bullosa. J Am Acad Dermatol. 2013 Jan;68(1):93–97, 97 e1–2.
   PubMed Web of Science ®Google Scholar
• van den Akker PC, Pasmooij AMG, Joenje H, et al. A “late-but-fitter revertant cell” explains the high frequency of revertant mosaicism in epidermolysis bullosa. PLoS One. 2018;13(2):e0192994.
   PubMed Web of Science ®Google Scholar
• Gostynski A, Pasmooij AMG, Jonkman MF. Successful therapeutic transplantation of revertant skin in epidermolysis bullosa. J Am Acad Dermatol. 2014;70(1):98–101.
   PubMed Web of Science ®Google Scholar
• Gostynski A, Deviaene FC, Pasmooij AM, et al. Adhesive stripping to remove epidermis in junctional epidermolysis bullosa for revertant cell therapy. Br J Dermatol. 2009 Aug;161(2):444–447.
   PubMed Web of Science ®Google Scholar
• Ghazizadeh S, Taichman LB. Multiple classes of stem cells in cutaneous epithelium: a lineage analysis of adult mouse skin. Embo J. 2001 Mar 15;20(6):1215–1222.
   PubMed Web of Science ®Google Scholar
• Blanpain C, Lowry WE, Geoghegan A, et al. Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell. 2004 Sep 3;118(5):635–648.
   PubMed Web of Science ®Google Scholar
• Fuchs E. Skin stem cells: rising to the surface. J Cell Biol. 2008 Jan 28;180(2):273–284.
   PubMed Web of Science ®Google Scholar
• Page ME, Lombard P, Ng F, et al. The epidermis comprises autonomous compartments maintained by distinct stem cell populations. Cell Stem Cell. 2013 Oct 3;13(4):471–482.
   PubMed Web of Science ®Google Scholar
• Barrandon Y, Green H. Three clonal types of keratinocyte with different capacities for multiplication. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2302–2306.
   PubMed Web of Science ®Google Scholar
• Beaver CM, Ahmed A, Masters JR. Clonogenicity: holoclones and meroclones contain stem cells. PLoS One. 2014;9(2):e89834.
   PubMed Web of Science ®Google Scholar
• Claudinot S, Nicolas M, Oshima H, et al. Long-term renewal of hair follicles from clonogenic multipotent stem cells. Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14677–14682.
   PubMed Web of Science ®Google Scholar
• De Rosa L, Secone Seconetti A, De Santis G, et al. Laminin 332-dependent YAP dysregulation depletes epidermal stem cells in junctional epidermolysis bullosa. Cell Rep. 2019 May 14;27(7):2036–2049 e6.
   PubMed Web of Science ®Google Scholar
• Dupont S. Role of YAP/TAZ in cell-matrix adhesion-mediated signalling and mechanotransduction. Exp Cell Res. 2016 Apr 10;343(1):42–53.
   PubMed Web of Science ®Google Scholar
• Dobrokhotov O, Samsonov M, Sokabe M, et al. Mechanoregulation and pathology of YAP/TAZ via Hippo and non-Hippo mechanisms. Clin Transl Med. 2018 Aug 13;7(1):23.
   PubMedGoogle Scholar
• Kim MK, Jang JW, Bae SC. DNA binding partners of YAP/TAZ. BMB Rep. 2018 Mar;51(3):126–133.
   PubMed Web of Science ®Google Scholar
• De Luca M, Pellegrini G, Green H. Regeneration of squamous epithelia from stem cells of cultured grafts. Regen Med. 2006 Jan;1(1):45–57.
   PubMed Web of Science ®Google Scholar
• Pellegrini G, Ranno R, Stracuzzi G, et al. The control of epidermal stem cells (holoclones) in the treatment of massive full-thickness burns with autologous keratinocytes cultured on fibrin. Transplantation. 1999 Sep 27;68(6):868–879.
   PubMed Web of Science ®Google Scholar
• Cuono C, Langdon R, McGuire J. Use of cultured epidermal autografts and dermal allografts as skin replacement after burn injury. Lancet. 1986 May 17;1(8490):1123–1124.
   PubMed Web of Science ®Google Scholar
• Petrof G, Abdul-Wahab A, Proudfoot L, et al. Serum levels of high mobility group box 1 correlate with disease severity in recessive dystrophic epidermolysis bullosa. Exp Dermatol. 2013 Jun;22(6):433–435.
   PubMed Web of Science ®Google Scholar
• Tamai K, Yamazaki T, Chino T, et al. PDGFRa-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia. PNAS. 2011;108(16):6609–6614.
   PubMed Web of Science ®Google Scholar
• Aikawa E, Fujita R, Kikuchi Y, et al. Systemic high-mobility group box 1 administration suppresses skin inflammation by inducing an accumulation of PDGFRalpha(+) mesenchymal cells from bone marrow. Sci Rep. 2015 Jun 5;5(1):11008.
   PubMedGoogle Scholar
• Badiavas EV, Abedi M, Butmarc J, et al. Participation of bone marrow derived cells in cutaneous wound healing. J Cell Physiol. 2003 Aug;196(2):245–250.
   PubMed Web of Science ®Google Scholar
• Kataoka K, Medina RJ, Kageyama T, et al. Participation of adult mouse bone marrow cells in reconstitution of skin. Am J Pathol. 2003 Oct;163(4):1227–1231.
   PubMed Web of Science ®Google Scholar
• Brittan M, Braun KM, Reynolds LE, et al. Bone marrow cells engraft within the epidermis and proliferate in vivo with no evidence of cell fusion. J Pathol. 2005 Jan;205(1):1–13.
   PubMed Web of Science ®Google Scholar
• Togel F, Westenfelder C. Adult bone marrow-derived stem cells for organ regeneration and repair. Dev Dyn. 2007 Dec;236(12):3321–3331.
   PubMed Web of Science ®Google Scholar
• Paunescu V, Deak E, Herman D, et al. In vitro differentiation of human mesenchymal stem cells to epithelial lineage. J Cell Mol Med. 2007 May-Jun;11(3):502–508.
   PubMed Web of Science ®Google Scholar
• Tolar J, Ishida-Yamamoto A, Riddle M, et al. Amelioration of epidermolysis bullosa by transfer of wild-type bone marrow cells. Blood. 2009 Jan 29;113(5):1167–1174.
   PubMed Web of Science ®Google Scholar
• Hunefeld C, Mezger M, Muller-Hermelink E, et al. Bone marrow-derived stem cells migrate into intraepidermal skin defects of a desmoglein-3 knockout mouse model but preserve their mesodermal differentiation. J Invest Dermatol. 2018 May;138(5):1157–1165. .
   PubMed Web of Science ®Google Scholar
• Kopp J, Horch RE, Stachel KD, et al. Hematopoietic stem cell transplantation and subsequent 80% skin exchange by grafts from the same donor in a patient with Herlitz disease. Transplantation. 2005 Jan 27;79(2):255–256.
   PubMed Web of Science ®Google Scholar
• Wagner JE, Ishida-Yamamoto A, McGrath JA, et al. Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. N Engl J Med. 2010 Aug 12;363(7):629–639.
   PubMed Web of Science ®Google Scholar
• Fujita Y, Abe R, Inokuma D, et al. Bone marrow transplantation restores epidermal basement membrane protein expression and rescues epidermolysis bullosa model mice. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14345–14350.
   PubMed Web of Science ®Google Scholar
• Petrof G, Martinez-Queipo M, Mellerio JE, et al. Fibroblast cell therapy enhances initial healing in recessive dystrophic epidermolysis bullosa wounds: results of a randomized, vehicle-controlled trial. Br J Dermatol. 2013 Nov;169(5):1025–1033.
   PubMed Web of Science ®Google Scholar
• Conget P, Rodriguez F, Kramer S, et al. Replenishment of type VII collagen and re-epithelialization of chronically ulcerated skin after intradermal administration of allogeneic mesenchymal stromal cells in two patients with recessive dystrophic epidermolysis bullosa. Cytotherapy. 2010 May;12(3):429–431.
   PubMed Web of Science ®Google Scholar
• Petrof G, Lwin SM, Martinez-Queipo M, et al. Potential of systemic allogeneic mesenchymal stromal cell therapy for children with recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2015 Sep;135(9):2319–2321.
   PubMed Web of Science ®Google Scholar
• El-Darouti M, Fawzy M, Amin I, et al. Treatment of dystrophic epidermolysis bullosa with bone marrow non-hematopoeitic stem cells: a randomized controlled trial. Dermatol Ther. 2016 Mar-Apr;29(2):96–100.
   PubMed Web of Science ®Google Scholar
• Rashidghamat E, Kadiyirire T, Ayis S, et al. Phase I/II open-label trial of intravenous allogeneic mesenchymal stromal cell therapy in adults with recessive dystrophic epidermolysis bullosa. J Am Acad Dermatol. 2019 Nov;28;Forthcoming(9):2020.
   Google Scholar
• Schatton T, Yang J, Kleffel S, et al. ABCD5 identifies immunoregulatory dermal cells. Cell Rep. 2015;12(10):1564–1574.
   PubMed Web of Science ®Google Scholar
• Jiang D, Muschhammer J, Qi Y, et al. Suppression of neutrophil-mediated tissue damage-a novel skill of mesenchymal stem cells. Stem Cells. 2016 Sep;34(9):2393–2406.
   PubMed Web of Science ®Google Scholar
• Webber BR, O’Connor KT, McElmurry RT, et al. Rapid generation of Col7a1(-/-) mouse model of recessive dystrophic epidermolysis bullosa and partial rescue via immunosuppressive dermal mesenchymal stem cells. Lab Invest. 2017 Oct;97(10):1218–1224.
   PubMed Web of Science ®Google Scholar
• Vander Beken S, De Vries JC, Meier-Schiesser B, et al. Newly defined ABCB5+ dermal mesenchymal stem cells promote healing of chronic iron overload wounds via secretion of interleukin-1 receptor antagonist. Stem Cells. 2019;37(8):1057–1074.
   PubMed Web of Science ®Google Scholar
• Karlsson H, Erkers T, Nava S, et al. Stromal cells from term fetal membrane are highly suppressive in allogeneic settings in vitro. Clin Exp Immunol. 2012 Mar;167(3):543–555.
   PubMed Web of Science ®Google Scholar
• Kaipe H, Carlson LM, Erkers T, et al. Immunogenicity of decidual stromal cells in an epidermolysis bullosa patient and in allogeneic hematopoietic stem cell transplantation patients. Stem Cells Dev. 2015 Jun 15;24(12):1471–1482.
   PubMed Web of Science ®Google Scholar
• Fine JD, Bruckner-Tuderman L, Eady RA, et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol. 2014 Jun;70(6):1103–1126.
   PubMed Web of Science ®Google Scholar
• Robbins PB, Lin Q, Goodnough JB, et al. In vivo restoration of laminin 5 beta 3 expression and function in junctional epidermolysis bullosa. Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5193–5198.
   PubMed Web of Science ®Google Scholar
• Robbins PB, Sheu SM, Goodnough JB, et al. Impact of laminin 5 beta3 gene versus protein replacement on gene expression patterns in junctional epidermolysis bullosa. Hum Gene Ther. 2001 Jul 20;12(11):1443–1448.
   PubMed Web of Science ®Google Scholar
• De Rosa L, Carulli S, Cocchiarella F, et al. Long-term stability and safety of transgenic cultured epidermal stem cells in gene therapy of junctional epidermolysis bullosa. Stem Cell Reports. 2014 Jan 14;2(1):1–8.
   PubMed Web of Science ®Google Scholar
• Grimm D, Lee JS, Wang L, et al. In vitro and in vivo gene therapy vector evolution via multispecies interbreeding and retargeting of adeno-associated viruses. J Virol. 2008 Jun;82(12):5887–5911.
   PubMed Web of Science ®Google Scholar
• Melo SP, Lisowski L, Bashkirova E, et al. Somatic correction of junctional epidermolysis bullosa by a highly recombinogenic AAV variant. Mol Ther. 2014 Apr;22(4):725–733.
   PubMed Web of Science ®Google Scholar
• Deyle DR, Russell DW. Adeno-associated virus vector integration. Curr Opin Mol Ther. 2009 Aug;11(4):442–447.
   PubMedGoogle Scholar
• Ivics Z, Hackett PB, Plasterk RH, et al. Molecular reconstruction of Sleeping Beauty, a Tc1-like transposon from fish, and its transposition in human cells. Cell. 1997 Nov 14;91(4):501–510.
   PubMed Web of Science ®Google Scholar
• Ortiz-Urda S, Lin Q, Yant SR, et al. Sustainable correction of junctional epidermolysis bullosa via transposon-mediated nonviral gene transfer. Gene Ther. 2003 Jul;10(13):1099–1104.
   PubMed Web of Science ®Google Scholar
• Ortiz-Urda S, Thyagarajan B, Keene DR, et al. PhiC31 integrase-mediated nonviral genetic correction of junctional epidermolysis bullosa. Hum Gene Ther. 2003 Jun 10;14(9):923–928.
   PubMed Web of Science ®Google Scholar
• Thyagarajan B, Olivares EC, Hollis RP, et al. Site-specific genomic integration in mammalian cells mediated by phage phiC31 integrase. Mol Cell Biol. 2001 Jun;21(12):3926–3934.
   PubMed Web of Science ®Google Scholar
• Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell. 2014 Jun 5;157(6):1262–1278.
   PubMed Web of Science ®Google Scholar
• Benati D, Miselli F, Cocchiarella F, et al. CRISPR/Cas9-mediated in situ correction of LAMB3 gene in keratinocytes derived from a junctional epidermolysis bullosa patient. Mol Ther. 2018 Nov 7;26(11):2592–2603.
   PubMed Web of Science ®Google Scholar
• Corrigan-Curay J, O’Reilly M, Kohn DB, et al. Genome editing technologies: defining a path to clinic. Mol Ther. 2015 May;23(5):796–806.
   PubMed Web of Science ®Google Scholar
• Kleinstiver BP, Pattanayak V, Prew MS, et al. High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature. 2016 Jan 28;529(7587):490–495.
   PubMed Web of Science ®Google Scholar
• Posteraro P, De Luca N, Meneguzzi G, et al. Laminin-5 mutational analysis in an Italian cohort of patients with junctional epidermolysis bullosa. J Invest Dermatol. 2004 Oct;123(4):639–648.
   PubMed Web of Science ®Google Scholar
• Yenamandra VK, Vellarikkal SK, Kumar M, et al. Application of whole exome sequencing in elucidating the phenotype and genotype spectrum of junctional epidermolysis bullosa: A preliminary experience of a tertiary care centre in India. J Dermatol Sci. 2017 Apr;86(1):30–36.
   PubMed Web of Science ®Google Scholar
• Fine JD, Johnson LB, Weiner M, et al. Epidermolysis bullosa and the risk of life-threatening cancers: the national EB registry experience, 1986-2006. J Am Acad Dermatol. 2009 Feb;60(2):203–211.
   PubMed Web of Science ®Google Scholar
• Virtanen I, Lohi J, Tani T, et al. Laminin chains in the basement membranes of human thymus. Histochem J. 1996 Sep;28(9):643–650.
   PubMedGoogle Scholar
• Mizushima H, Koshikawa N, Moriyama K, et al. Wide distribution of laminin-5 gamma 2 chain in basement membranes of various human tissues. Hormone Res. 1998;50(2):7–14.
   PubMedGoogle Scholar
• Kim MG, Lee G, Lee SK, et al. Epithelial cell-specific laminin 5 is required for survival of early thymocytes. J Immunol. 2000 Jul 1;165(1):192–201.
   PubMed Web of Science ®Google Scholar
• Vivinus-Nebot M, Rousselle P, Breittmayer JP, et al. Mature human thymocytes migrate on laminin-5 with activation of metalloproteinase-14 and cleavage of CD44. J Immunol. 2004 Feb 1;172(3):1397–1406.
   PubMed Web of Science ®Google Scholar