TY - JOUR
T1 - Gene therapies for inherited skin disorders
AU - Abdul-Wahab, Alya
AU - Qasim, Waseem
AU - McGrath, John A.
N1 - Publisher Copyright:
© 2014 Frontline Medical Communications.
PY - 2014/6/1
Y1 - 2014/6/1
N2 - Skin is an amenable organ for gene replacement and gene editing therapeutics. Its accessibility makes it wellsuited for direct topical gene delivery, grafting of genetically corrected cells, and monitoring of possible adverse events. Monogenic recessive disorders with a clinically severe or life-threatening phenotype provide the best candidate diseases for the introduction of a single normal copy of the gene into the target cell, usually keratinocytes. Preclinical studies have shown impressive results in terms of gene correction using both in vivo and ex vivo approaches. The clinical application of gene replacement or genomic editing as potential therapies for inherited skin disorders, however, has been held back by the inadequacy of delivery vectors and concerns from regulatory agencies regarding safety; thus translation to clinical trials has been slow. Over the past 15 years, cell culture and animal models have shown efficient gene correction techniques as preludes to treat inherited skin disorders such as junctional epidermolysis bullosa, dystrophic epidermolysis bullosa, xeroderma pigmentosum, lamellar ichthyosis and Netherton syndrome, but so far only one patient has been treated in a clinical trial. This article reviews the current status of gene therapies for patients with inherited skin diseases and explores future perspectives.
AB - Skin is an amenable organ for gene replacement and gene editing therapeutics. Its accessibility makes it wellsuited for direct topical gene delivery, grafting of genetically corrected cells, and monitoring of possible adverse events. Monogenic recessive disorders with a clinically severe or life-threatening phenotype provide the best candidate diseases for the introduction of a single normal copy of the gene into the target cell, usually keratinocytes. Preclinical studies have shown impressive results in terms of gene correction using both in vivo and ex vivo approaches. The clinical application of gene replacement or genomic editing as potential therapies for inherited skin disorders, however, has been held back by the inadequacy of delivery vectors and concerns from regulatory agencies regarding safety; thus translation to clinical trials has been slow. Over the past 15 years, cell culture and animal models have shown efficient gene correction techniques as preludes to treat inherited skin disorders such as junctional epidermolysis bullosa, dystrophic epidermolysis bullosa, xeroderma pigmentosum, lamellar ichthyosis and Netherton syndrome, but so far only one patient has been treated in a clinical trial. This article reviews the current status of gene therapies for patients with inherited skin diseases and explores future perspectives.
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U2 - 10.12788/j.sder.0085
DO - 10.12788/j.sder.0085
M3 - Article
C2 - 25085667
AN - SCOPUS:84907939314
SN - 1085-5629
VL - 33
SP - 83
EP - 90
JO - Seminars in Cutaneous Medicine and Surgery
JF - Seminars in Cutaneous Medicine and Surgery
IS - 2
ER -