Gene Silencing in Skin After Deposition of Self-Delivery siRNA With a Motorized Microneedle Array Device

被引：22

作者：

Hickerson, Robyn P. ^{[1
]}

Wey, Winston C. ^{[2
]}

Rimm, David L. ^{[3
]}

Speaker, Tycho ^{[1
]}

Suh, Susie ^{[2
]}

Flores, Manuel A. ^{[1
]}

Gonzalez-Gonzalez, Emilio ^{[2
]}

Leake, Devin ^{[4
]}

Contag, Christopher H. ^{[2
]}

Kaspar, Roger L. ^{[1
]}

机构：

[1] TransDerm, Santa Cruz, CA 95060 USA

[2] Stanford Univ Sch Med, Dept Pediat Radiol & Microbiol & Immunol, Stanford, CA USA

[3] Yale Univ Sch Med, Dept Pathol, New Haven, CT USA

[4] Dharmacon Prod, Thermo Fisher Sci, Lafayette, CO USA

来源：

MOLECULAR THERAPY-NUCLEIC ACIDS | 2013年 / 2卷

基金：

美国国家卫生研究院;

关键词：

gene inhibition; nucleic acid therapeutics; reporter genes; siRNA delivery; RNA INTERFERENCE; FORMALIN TEST; EXPRESSION; MOUSE; PAIN; DISORDERS; DNA;

D O I：

10.1038/mtna.2013.56

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页数：7

共 32 条

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