Activation of "caged" oligonucleotides by red light

光诱导基因敲减是一种有效的基因功能调控方法。在该方法中，使用寡核苷酸，其与核酸的结合由光触发（“笼状”寡核苷酸）。光诱导基因敲除的全部潜力尚未完全实现，因为只有紫外光敏感的“笼状”试剂可用。紫外线具有高度致突变性和毒性。这些副作用掩盖了“笼状”寡核苷酸的特异性生物活性。如果基因敲低的光引发可以使用无毒的红光完成，该方法将在分子生物学和医学中找到更广泛的应用。特别是，触发基因敲除可以在组织的深层区域进行，因为红光被细胞成分微弱吸收。相比之下，UV光被例如细胞中丰富的蛋白质和核酸强烈吸收，因此它可能仅影响组织的表面区域。该项目的目的是获得“笼”试剂（DNA和RNA），其生物活性（反义或RNAi）可以通过暴露于红光来触发。

Light-induced gene knockdown is a powerful approach for determination and control of gene functions. In this method oligonucleotides are used, whose binding to nucleic acids is triggered by light (“caged” oligonucleotides). The full potential of light-induced gene knockdown is not yet fully realized, because only UV-light sensitive “caged” reagents are available. UV-light is highly mutagenic and toxic. These side effects mask specific biological activity of “caged” oligonucleotides. Providing photoinitiation of gene knockdown could be done using non-toxic red light, the method would find much broader applications in molecular biology and medicine. In particular, triggering gene-knockdown could be performed in deep regions of tissues, since red light is weakly absorbed by cellular components. In contrast, UV-light is strongly absorbed by e.g. abundant proteins and nucleic acids in cells, therefore it may affect only surface regions of tissues. The aim of this project is to obtain “caged” reagents (DNAs and RNAs), whose biological activity (antisense or RNAi) can be triggered by exposure to red light.