Original Article

Subject Category: Genetics

Journal of Investigative Dermatology (2007) 127, 2577–2584; doi:10.1038/sj.jid.5700891; published online 24 May 2007

Delivery and Inhibition of Reporter Genes by Small Interfering RNAs in a Mouse Skin Model

Qian Wang1,2, Heini Ilves3, Pauline Chu4, Christopher H Contag1,2, Devin Leake5, Brian H Johnston2,3 and Roger L Kaspar3,6

  1. 1Molecular Imaging Program at Stanford (MIPS), and Departments of Radiology, Microbiology & Immunology, Stanford University School of Medicine, Stanford, California, USA
  2. 2Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA
  3. 3SomaGenics Inc., Santa Cruz, California, USA
  4. 4Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
  5. 5Thermo Fisher Scientific, Dharmacon Products, Lafayette, Colorado, USA
  6. 6TransDerm, Santa Cruz, California, USA

Correspondence: Dr Roger L. Kaspar, TransDerm Inc., 2161 Delaware Avenue, Santa Cruz, California 95060, USA. E-mail: Roger.Kaspar@TransDermInc.com

Received 9 September 2006; Revised 28 February 2007; Accepted 27 March 2007; Published online 24 May 2007.

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Abstract

RNA interference offers the potential of a novel therapeutic approach for treating skin disorders. To this end, we investigated delivery of nucleic acids, including a plasmid expressing the reporter gene luciferase, to mouse skin by intradermal injection into footpads using in vivo bioluminescence imaging over multiple time points. In order to evaluate the ability of RNA interference to inhibit skin gene expression, reporter gene constructs were co-injected with specific or non-specific siRNAs and the in vivo effects measured. Our results revealed that specific unmodified and modified siRNAs (but not nonspecific matched controls) strongly inhibit reporter gene expression in mice. These results indicate that small interfering RNA, delivered locally as RNA directly or expressed from viral or non-viral vectors, may be effective agents for treating skin disorders.

Abbreviations:

beta-gal, beta-galactosidase; CMV, cytomegalovirus; EF1A, elongation factor 1A; eGFP, enhanced green fluorescent protein; fLuc, firefly luciferase; FMDV, foot and mouth disease virus; IP, intraperitoneal; KBM, keratinocyte basal medium; PC, pachyonychia congenita; SEAP, secreted alkaline phosphatase; siRNA, small interfering RNA

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