Wang Qian, Ilves Heini, Chu Pauline, Contag Christopher H, Leake Devin, Johnston Brian H, Kaspar Roger L
Molecular Imaging Program at Stanford, and Department of Radiology, Stanford University School of Medicine, Stanford, California, USA.
J Invest Dermatol. 2007 Nov;127(11):2577-84. doi: 10.1038/sj.jid.5700891. Epub 2007 May 24.
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.
RNA干扰为治疗皮肤疾病提供了一种新型治疗方法的潜力。为此，我们通过在多个时间点使用体内生物发光成像技术，将包括表达报告基因荧光素酶的质粒在内的核酸经皮内注射到脚垫，研究其向小鼠皮肤的递送情况。为了评估RNA干扰抑制皮肤基因表达的能力，将报告基因构建体与特异性或非特异性小干扰RNA（siRNA）共同注射，并测量体内效应。我们的结果显示，特异性未修饰和修饰的siRNA（而非非特异性匹配对照）能强烈抑制小鼠体内报告基因的表达。这些结果表明，作为RNA直接局部递送或从病毒或非病毒载体表达的小干扰RNA，可能是治疗皮肤疾病的有效药物。
