Nucleic acid delivery to skin for the potential treatment of dermatopathogenic conditions [Abstract]

Chong, Rosalind, Coulman, Sion ORCID: https://orcid.org/0000-0002-1277-7584, Saller, V., Pearton, Marc, Shah, A., Hargest, Rachel ORCID: https://orcid.org/0000-0001-9830-3832 and Birchall, James Caradoc ORCID: https://orcid.org/0000-0001-8521-6924 2011. Nucleic acid delivery to skin for the potential treatment of dermatopathogenic conditions [Abstract]. Human Gene Therapy 22 (10) , A82-A82.

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Abstract

The delivery of nucleic acid therapies to their intracellular target site is one of the greatest challenges in gene therapy. In human skin this challenge is further complicated by the presence of the outermost barrier layer, the stratum corneum. We aim to optimise a method for delivery of nucleic acid therapies into the skin using microneedle device (MN) technology, with a view to influencing the pathogenesis of inflamed dermatopathogenic conditions such as pyoderma gangrenosum. The ability to dry coat a siRNA formulation onto MNs was investigated using Lamin A/C as a model gene for knockdown studies. Immortalised human keratinocytes (HaCaT cells) and primary keratinocytes, isolated and cultured from excised human breast skin, were used to evaluate the functionality ofMN loaded siRNA. RNA interference (RNAi) activity was evaluated through polymerase chain reaction (PCR) for gene expression, western blotting for protein synthesis and confocal microscopy for visualisation of cell protein immunofluorescence. Up to 30mg siRNA was successfully dry-coated onto the surface of MNs. The coating and drying process did not appear to reduce the biological functionality of siRNA, demonstrated by the significant reduction in gene expression/protein synthesis of Lamin A/C in both HaCaT and primary keratinocyte cells. Current studies are using MNs as a minimally invasive method to facilitate effective cutaneous delivery of siRNA to human skin explants and in vivo models and we are encouraged by our preliminary experiments where dry-coated pDNA (100mg; pCMVb) has been successfully delivered, and subsequently expressed, in human skin explants using MNs.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Publisher:	Mary Ann Liebert
ISSN:	1043-0342
Last Modified:	07 Nov 2022 08:35
URI:	https://orca.cardiff.ac.uk/id/eprint/32376

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