In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial - Nature Medicine

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In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial - Nature Medicine
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Preclinical data and results from a phase 1/2 trial demonstrate preliminary safety and efficacy of topically-administered genetherapy for recessive dystrophic EpidermolysisBullosa StanfordMed KrystalBiotech debraOfAmerica EBResearch EBawareness

, the durability of B-VEC wound closure is anticipated to last around 12 weeks. This expectation informed the timepoint selection for analysis . Based on a responder definition of complete wound closure for at least 2 consecutive weeks , responder analysis comparison of the incidence of complete wound closure between B-VEC-treated wounds and placebo-treated wounds was performed on observed data .

. These were established from a breeding pair donated by L. Bruckner-Tuderman . Mice were genotyped with DNA extracted from an ear punch tissue sample. PCR analysis detected the presence of a loxP site upstream of exon 2 of. Wild-type mice show a band at 269 bp and hypomorph mice show the band at 435 bp, while heterozygous mice have both. Balb/C mice were obtained from The Jackson Laboratory. For xenografting, NOD/SCID mice were used .

For intradermal injections the animal’s back was shaved and the mouse was injected at four sites on the back, consisting of one control vehicle injection and three B-VEC injections. Intradermal injections were performed using the Mantoux technique with a 31 G BD SafetyGlide 0.3 ml insulin syringe, ensuring creation of a superficial wheal at each site. Up to four intradermal injections were given to the back of each mouse at the doses specified in the Results section.

. All imaging and image processing , including tiling of the images, was done using AxioVision SE64 v4.9.1 by Zeiss.

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