Clinical Perspectives of Gene-Targeted Therapies for Epidermolysis Bullosa.

Antisense oligonucleotides Epidermolysis bullosa Gene editing Gene replacement Gene therapy Readthrough Trans-splicing siRNA

Journal

Dermatology and therapy
ISSN: 2193-8210
Titre abrégé: Dermatol Ther (Heidelb)
Pays: Switzerland
ID NLM: 101590450

Informations de publication

Date de publication:
Aug 2021
Historique:
received: 08 04 2021
pubmed: 11 6 2021
medline: 11 6 2021
entrez: 10 6 2021
Statut: ppublish

Résumé

New insights into molecular genetics and pathomechanisms in epidermolysis bullosa (EB), methodological and technological advances in molecular biology as well as designated funding initiatives and facilitated approval procedures for orphan drugs have boosted translational research perspectives for this devastating disease. This is echoed by the increasing number of clinical trials assessing innovative molecular therapies in the field of EB. Despite remarkable progress, gene-corrective modalities, aimed at sustained or permanent restoration of functional protein expression, still await broad clinical availability. This also reflects the methodological and technological shortcomings of current strategies, including the translatability of certain methodologies beyond preclinical models as well as the safe, specific, efficient, feasible, sustained and cost-effective delivery of therapeutic/corrective information to target cells. This review gives an updated overview on status, prospects, challenges and limitations of current gene-targeted therapies.

Identifiants

DOI: 10.1007/s13555-021-00561-5 PMID: 34110606 PMC: PMC8322229
pubmed: 34110606
doi: 10.1007/s13555-021-00561-5
pii: 10.1007/s13555-021-00561-5
pmc: PMC8322229
doi:

Types de publication

Journal Article Review

Langues

eng

Pagination

1175-1197

Informations de copyright

© 2021. The Author(s).

Références

JCI Insight. 2019 Jun 6;4(11):
pubmed: 31167965
J Am Acad Dermatol. 2020 Aug;83(2):447-454
pubmed: 31786163
Mol Diagn Ther. 2020 Jun;24(3):299-309
pubmed: 32328988
Orphanet J Rare Dis. 2020 Jul 10;15(1):182
pubmed: 32650809
Hum Mol Genet. 2010 Dec 1;19(23):4715-25
pubmed: 20861136
Nucleic Acids Res. 2021 Apr 19;49(7):3692-3708
pubmed: 33764477
Orphanet J Rare Dis. 2012 Aug 31;7:58
pubmed: 22938201
Acta Derm Venereol. 2020 Jul 2;100(220):
pubmed: 32617601
J Invest Dermatol. 2012 May;132(5):1374-83
pubmed: 22318390
J Invest Dermatol. 2011 Oct;131(10):2079-86
pubmed: 21716320
Br J Dermatol. 2020 Mar;182(3):794-797
pubmed: 31557321
J Clin Invest. 2008 May;118(5):1669-79
pubmed: 18382769
JCI Insight. 2021 Jan 25;6(2):
pubmed: 33491668
Trends Mol Med. 2014 Nov;20(11):604-13
pubmed: 25263172
Cells. 2020 Jan 02;9(1):
pubmed: 31906492
J Clin Invest. 2007 May;117(5):1240-8
pubmed: 17476356
Nat Med. 2004 Jul;10(7):693-5
pubmed: 15195089
J Invest Dermatol. 2011 Aug;131(8):1771-4
pubmed: 21471992
Skin Pharmacol Physiol. 2021;34(4):167-182
pubmed: 33823521
J Eur Acad Dermatol Venereol. 2020 Sep;34(9):1879-1880
pubmed: 33448527
Cold Spring Harb Perspect Biol. 2020 May 1;12(5):
pubmed: 31653644
Br J Dermatol. 2016 May;174(5):1122-5
pubmed: 26595603
Dermatology. 2019;235(4):315-322
pubmed: 31132778
Cytotherapy. 2010 May;12(3):429-31
pubmed: 20230217
Dermatol Ther. 2016 Mar-Apr;29(2):96-100
pubmed: 26439431
Orphanet J Rare Dis. 2010 May 28;5:12
pubmed: 20507631
Br Med Bull. 2020 Dec 15;136(1):4-20
pubmed: 33010155
J Eur Acad Dermatol Venereol. 2020 Sep;34(9):2127-2134
pubmed: 32124492
Exp Dermatol. 2020 Nov;29(11):1112-1122
pubmed: 33043517
Trends Genet. 2008 Nov;24(11):552-63
pubmed: 18937996
Proc Natl Acad Sci U S A. 2019 Dec 26;116(52):26846-26852
pubmed: 31818947
Front Genet. 2021 Apr 30;12:658295
pubmed: 33995490
Mol Ther Nucleic Acids. 2016 Oct 18;5(10):e379
pubmed: 27754488
Br J Dermatol. 2013 Nov;169(5):1025-33
pubmed: 24032424
Br J Dermatol. 2009 Aug;161(2):444-7
pubmed: 19416258
Mol Ther. 2020 May 6;28(5):1327-1338
pubmed: 32222156
Mol Ther Nucleic Acids. 2016 Mar 01;5:e287
pubmed: 26928235
Br J Dermatol. 2013 Jul;169(1):115-24
pubmed: 23496044
Mol Ther. 2018 Nov 7;26(11):2592-2603
pubmed: 30122422
Exp Dermatol. 2016 Oct;25(10):818-20
pubmed: 27117059
J Am Acad Dermatol. 2014 Jan;70(1):98-101
pubmed: 24176523
Proc Natl Acad Sci U S A. 1986 May;83(10):3194-8
pubmed: 3458176
Nature. 2017 Nov 16;551(7680):327-332
pubmed: 29144448
J Am Acad Dermatol. 2012 Nov;67(5):904-17
pubmed: 22387035
J Invest Dermatol. 2013 Dec;133(12):2793-2796
pubmed: 23743647
PLoS One. 2018 Feb 22;13(2):e0192994
pubmed: 29470523
Br J Dermatol. 2019 Dec;181(6):1238-1246
pubmed: 30843184
J Clin Invest. 1999 Aug;104(4):375-81
pubmed: 10449429
Cell Rep. 2019 May 14;27(7):2036-2049.e6
pubmed: 31091444
Mol Ther. 2014 Oct;22(10):1741-52
pubmed: 25155989
J Clin Invest. 2017 Aug 1;127(8):3028-3038
pubmed: 28691931
J Invest Dermatol. 2017 Sep;137(9):1842-1849
pubmed: 28549954
J Invest Dermatol. 2006 Dec;126(12):2614-20
pubmed: 16778792
J Invest Dermatol. 2019 Oct;139(10):2115-2124.e11
pubmed: 31054844
JCI Insight. 2019 Oct 3;4(19):
pubmed: 31578311
Exp Dermatol. 2021 May;30(5):664-675
pubmed: 33595864
Medicine (Baltimore). 2015 Oct;94(42):e1528
pubmed: 26496255
PLoS Genet. 2019 Mar 14;15(3):e1007994
pubmed: 30870431
NPJ Regen Med. 2016;1:
pubmed: 28250968
Br J Dermatol. 2019 Dec;181(6):1247-1253
pubmed: 30924923
J Invest Dermatol. 2016 Oct;136(10):2093-2095
pubmed: 27283508
Mol Ther Nucleic Acids. 2019 Dec 6;18:465-475
pubmed: 31670143
J Invest Dermatol. 2013 Jul;133(7):1901-3
pubmed: 23344459
Sci Transl Med. 2014 Nov 26;6(264):264ra163
pubmed: 25429056
J Invest Dermatol. 2008 Sep;128(9):2179-89
pubmed: 18385758
J Invest Dermatol. 2012 Jun;132(6):1741-3
pubmed: 22336946
J Cell Biol. 2001 Feb 5;152(3):651-6
pubmed: 11157990
J Invest Dermatol. 2003 Nov;121(5):1021-8
pubmed: 14708601
Mol Ther Nucleic Acids. 2019 Dec 6;18:496-507
pubmed: 31670199
Proc Natl Acad Sci U S A. 1987 Apr;84(8):2302-6
pubmed: 2436229
J Am Acad Dermatol. 2013 Dec;69(6):898-908.e7
pubmed: 24075228
Mol Ther. 2016 Aug;24(7):1302-11
pubmed: 27157667
Mol Ther. 2021 Jun 2;29(6):2008-2018
pubmed: 33609734
J Invest Dermatol. 2021 Apr;141(4):883-893.e6
pubmed: 32946877
Mol Ther Methods Clin Dev. 2017 Jul 05;6:112-123
pubmed: 28765827
EMBO Mol Med. 2015 Jul 20;7(9):1211-28
pubmed: 26194911
J Invest Dermatol. 2013 Jul;133(7):1910-3
pubmed: 23321924
PLoS One. 2013 Jul 08;8(7):e67609
pubmed: 23861776
Exp Dermatol. 2019 Oct;28(10):1176-1189
pubmed: 31140655
J Am Acad Dermatol. 2009 Sep;61(3):387-402; quiz 403-4
pubmed: 19700011
J Invest Dermatol. 2015 Sep;135(9):2319-2321
pubmed: 25905587
J Invest Dermatol. 2016 Dec;136(12):2387-2395
pubmed: 27498345
J Dermatol Sci. 2020 Jun;98(3):163-172
pubmed: 32376152
Hum Vaccin. 2008 Mar-Apr;4(2):91-105
pubmed: 18496918
Orphanet J Rare Dis. 2019 Jun 7;14(1):129
pubmed: 31174559
J Biol Chem. 2009 Oct 30;284(44):30248-56
pubmed: 19726672
Orphanet J Rare Dis. 2021 Apr 13;16(1):175
pubmed: 33849616
BMC Med. 2014 Oct 09;12:178
pubmed: 25603875
Am J Pathol. 2017 Jul;187(7):1445-1453
pubmed: 28460207
J Invest Dermatol. 2000 Aug;115(2):332
pubmed: 10951258
J Am Acad Dermatol. 2009 Sep;61(3):367-84; quiz 385-6
pubmed: 19700010
J Clin Invest. 2003 Jan;111(2):251-5
pubmed: 12531881
Mol Ther. 2009 Jan;17(1):26-33
pubmed: 19018253
Mol Ther. 2013 Jun;21(6):1151-9
pubmed: 23546300
J Med Genet. 2011 Jul;48(7):450-7
pubmed: 21357940
Cell Transplant. 2019 Sep-Oct;28(9-10):1242-1256
pubmed: 31271052
Hum Mol Genet. 2014 Aug 1;23(15):3907-22
pubmed: 24599399
J Invest Dermatol. 2008 Mar;128(3):568-74
pubmed: 17989727
J Dermatol. 2020 Mar;47(3):e82-e83
pubmed: 31919892
J Invest Dermatol. 1999 Sep;113(3):314-21
pubmed: 10469327
Mol Ther. 2017 Nov 1;25(11):2573-2584
pubmed: 28800953
J Invest Dermatol. 2010 Jul;130(7):1937-40
pubmed: 20357813
Stem Cells. 2021 Jul;39(7):897-903
pubmed: 33609408
Int J Mol Sci. 2016 Sep 24;17(10):
pubmed: 27669234
Clin Exp Ophthalmol. 2021 Apr;49(3):309-312
pubmed: 33634938
Stem Cell Reports. 2013 Dec 26;2(1):1-8
pubmed: 24511464
Sci Transl Med. 2014 Nov 26;6(264):264ra164
pubmed: 25429057
Br J Dermatol. 2020 Oct;183(4):614-627
pubmed: 32017015
J Virol. 1998 Dec;72(12):9873-80
pubmed: 9811723
Mol Ther. 2017 Nov 1;25(11):2585-2598
pubmed: 28888469
J Invest Dermatol. 2017 Mar;137(3):778-781
pubmed: 27840234
Cancer Res. 2012 Jul 15;72(14):3522-34
pubmed: 22564523
ACS Appl Mater Interfaces. 2019 Aug 28;11(34):30661-30672
pubmed: 31390173
J Invest Dermatol. 2011 Jan;131(1):74-83
pubmed: 20720561
J Invest Dermatol. 2019 Jun;139(6):1221-1226
pubmed: 31068252
Nat Med. 2006 Dec;12(12):1397-402
pubmed: 17115047
Br J Dermatol. 2019 Feb;180(2):357-364
pubmed: 29932457
Methods Mol Biol. 2013;961:441-55
pubmed: 23325663
Crit Rev Biotechnol. 2017 Aug;37(5):672-684
pubmed: 27535623

Auteurs

Tobias Welponer (T)

Department of Dermatology and Allergology and EB House Austria, University Hospital of the Paracelsus Medical University, Salzburg, Austria.

Christine Prodinger (C)

Department of Dermatology and Allergology and EB House Austria, University Hospital of the Paracelsus Medical University, Salzburg, Austria.

Josefina Pinon-Hofbauer (J)

Department of Dermatology and Allergology and EB House Austria, University Hospital of the Paracelsus Medical University, Salzburg, Austria.

Arno Hintersteininger (A)

Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, Salzburg, Austria.

Hannelore Breitenbach-Koller (H)

Department of Biosciences, Paris Lodron University of Salzburg, Salzburg, Austria.

Johann W Bauer (JW)

Department of Dermatology and Allergology and EB House Austria, University Hospital of the Paracelsus Medical University, Salzburg, Austria.
Department of Biosciences, Paris Lodron University of Salzburg, Salzburg, Austria.

Martin Laimer (M)

Department of Dermatology and Allergology and EB House Austria, University Hospital of the Paracelsus Medical University, Salzburg, Austria. m.laimer@salk.at.

Classifications MeSH