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.
Semin Cutan Med Surg 33:83-90 © 2014 Frontline Medical
CommunicationsSkin 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.
Semin Cutan Med Surg 33:83-90 © 2014 Frontline Medical
Communications