title: Gene Silencing in Skin After Deposition of Self-Delivery siRNA With a Motorized Microneedle Array Device.
abstract: Despite the development of potent siRNAs that effectively target genes responsible for skin disorders, translation to the clinic has been hampered by inefficient delivery through the stratum corneum barrier and into the live cells of the epidermis. Although hypodermic needles can be used to transport siRNA through the stratum corneum, this approach is limited by pain caused by the injection and the small volume of tissue that can be accessed by each injection. The use of microneedle arrays is a less painful method for siRNA delivery, but restricted payload capacity limits this approach to highly potent molecules. To address these challenges, a commercially available motorized microneedle array skin delivery device was evaluated. This device combines the positive elements of both hypodermic needles and microneedle array technologies with little or no pain to the patient. Application of fluorescently tagged self-delivery (sd)-siRNA to both human and murine skin resulted in distribution throughout the treated skin. In addition, efficient silencing (78% average reduction) of reporter gene expression was achieved in a transgenic fluorescent reporter mouse skin model. These results indicate that this device effectively delivers functional sd-siRNA with an efficiency that predicts successful clinical translation.Molecular Therapy-Nucleic Acids (2013) 2, e129; doi:10.1038/mtna.2013.56; published online 22 October 2013.
authors.affiliation: 1] TransDerm, Santa Cruz, California, USA [2] Current address: University of Dundee, Dundee, UK.
authors.forename: Robyn P
authors.initials: RP
authors.lastname: Hickerson
authors.forename: Winston C
authors.initials: WC
authors.lastname: Wey
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
authors.forename: Tycho
authors.initials: T
authors.lastname: Speaker
authors.forename: Susie
authors.initials: S
authors.lastname: Suh
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Flores
authors.forename: Emilio
authors.initials: E
authors.lastname: Gonzalez-Gonzalez
authors.forename: Devin
authors.initials: D
authors.lastname: Leake
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Contag
authors.forename: Roger L
authors.initials: RL
authors.lastname: Kaspar