Cutaneous DNA delivery and gene expression in ex vivo human skin explants via wet-etch micro-fabricated micro-needles.

Abstract:

:Micro-needle arrays increase skin permeability by forming channels through the outer physical barrier, without stimulating pain receptors populating the underlying dermis. It was postulated that micro-needle arrays could facilitate transfer of DNA to human skin epidermis for cutaneous gene therapy applications. Platinum-coated "wet-etch" silicon micro-needles were shown to be of appropriate dimensions to create micro-conduits, approximately 50 microm in diameter, extending through the stratum corneum (SC) and viable epidermis. Following optimisation of skin explant culturing techniques and confirmation of tissue viability, the ability of the micro-needles to mediate gene expression was demonstrated using the beta-galactosidase reporter gene. Preliminary studies confirmed localised delivery, cellular internalisation and subsequent gene expression of pDNA following micro-needle disruption of skin. A combination of this innovative gene delivery platform and the ex vivo skin culture model will be further exploited to optimise cutaneous DNA delivery and address fundamental questions regarding gene expression in skin.

journal_name

J Drug Target

authors

Birchall J,Coulman S,Pearton M,Allender C,Brain K,Anstey A,Gateley C,Wilke N,Morrissey A

doi

10.1080/10611860500383705

keywords:

subject

Has Abstract

pub_date

2005-08-01 00:00:00

pages

415-21

issue

7

eissn

1061-186X

issn

1029-2330

pii

M34X12311181V373

journal_volume

13

pub_type

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