RNA interference (RNAi) mediated gene silencing holds significant promise in gene therapy. It is very important to manually regulate the activity of small interference RNAs (siRNAs) in the controllable mode. Here, we designed and synthesized a series of caged siRNAs through bioconjugation of cyclo(Arg-Gly-Asp-d-Phe-Lys) (cRGD) peptide to the 5′ end of siRNA through a photolabile linker. These cRGD modified caged siRNAs allowed for precise light-regulation of gene expression of two exogenous reporter genes (firefly luciferase and green fluorescent protein, GFP) and an endogenous gene (the mitosis motor protein, Eg5) in the integrin α_vβ₃ positive cells. This kind of bioconjugate further enabled photochemical activation of siRNA activity, and the target gene silencing was successfully achieved in tumor-bearing mice by intratumoral injection. This study also suggested that photomodulation of target gene expression using single cRGD caged siRNA at the 5′ end of antisense strand RNA inhibited siRNA activity probably due to three factors: (1) trapping of cRGD modified siRNA in endosome and lysosome, (2) the steric hindrance of cRGD, (3) the binding of cRGD to its corresponding receptor.

中文翻译：

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具有单个cRGD修饰的笼状siRNA，用于光调节细胞和小鼠中外源和内源基因的表达

RNA干扰（RNAi）介导的基因沉默在基因治疗中具有重大前景。以可控方式手动调节小干扰RNA（siRNA）的活性非常重要。在这里，我们通过光不稳定的接头将环（Arg-Gly-Asp- d -Phe-Lys）（cRGD）肽生物缀合至siRNA的5'端，设计并合成了一系列笼状siRNA 。这些修饰的cRGD笼允许在两个外源报道基因（萤火虫荧光素酶和绿色荧光蛋白，GFP）和内源基因（有丝分裂驱动蛋白，Eg5的）基因表达的精确光调节整合素α的siRNA _v β ₃阳性细胞。这种生物共轭物进一步实现了siRNA活性的光化学活化，并且通过瘤内注射在荷瘤小鼠中成功实现了靶基因沉默。这项研究还表明，在反义链RNA 5'端使用单个cRGD笼状siRNA进行靶基因表达的光调节可抑制siRNA活性，这可能归因于以下三个因素：（1）将cRGD修饰的siRNA捕获在内体和溶酶体中，（2） cRGD的空间位阻，（3）cRGD与其相应受体的结合。