In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 9 ( 2001-04-24), p. 5193-5198
Abstract:
The blistering disorder, lethal junctional epidermolysis bullosa
(JEB), can result from mutations in the LAMB3 gene,
which encodes laminin 5 β3 (β3). Appropriate expression of LAMβ3 in JEB skin tissue could potentially ameliorate the symptoms of the
underlying disease. To explore the utility of this therapeutic approach, primary keratinocytes from six unrelated JEB patients were
transduced with a retroviral vector encoding β3 and used to regenerate human skin on severe combined immunodeficient (SCID) mice.
Tissue regenerated from β3-transduced JEB keratinocytes produced phenotypically normal skin characterized by sustained β3 expression
and the formation of hemidesmosomes. Additionally, β3 gene transfer corrected the distribution of a number of important basement membrane
zone proteins including BPAG2, integrins β4/β1, and laminins α3/γ2. Skin produced from β3-negative (β3[−]) JEB cells mimicked the hallmarks of the disease state and did not exhibit
any of the aforementioned traits. Therefore, by effecting therapeutic gene transfer to β3-deficient primary keratinocytes, it is possible
to produce healthy, normal skin tissue in vivo . These
data support the utility of gene therapy for JEB and highlight the potential for gene delivery in the treatment of human genetic skin
disease.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.091484998
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2001
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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