Zhou Jiehua, Rossi John J, Shum Ka To
Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA, USA.
Methods Mol Biol. 2015;1297:169-85. doi: 10.1007/978-1-4939-2562-9_12.
Structured functional RNA entities, including aptamers and siRNAs, have amazing versatility in structure and function. These molecules can serve as powerful, attractive building blocks for the bottom-up assembly of complex nanostructures. Here, we describe novel cell-type specific and internalizing B-cell activating factor receptor (BAFF-R) aptamer-siRNA delivery systems for B-cell lymphoma therapy, in which both the aptamer and the Dicer substrate siRNA (DsiRNA) portions are conjugated through a "sticky bridge." The BAFF-R is overexpressed on the surface of B-cell malignancies, allowing binding and internalization of the aptamer-stick-siRNA nanoparticles. STAT3 siRNAs are encapsulated within the nanoparticles delivered by the BAFF-R aptamers and are localized to the cytoplasm, resulting in robust gene silencing of STAT3 mRNAs in a variety of B-cell lines. Moreover, these nanoparticles do not induce cell proliferation and apoptosis. Collectively, aptamer-mediated delivery strategies provide a toolset to become a more widely used therapeutic modality for the treatment of diseases.
包括适体和小干扰RNA（siRNA）在内的结构化功能性RNA实体在结构和功能上具有惊人的多功能性。这些分子可作为强大且有吸引力的构建模块，用于自下而上地组装复杂的纳米结构。在此，我们描述了用于B细胞淋巴瘤治疗的新型细胞类型特异性且可内化的B细胞活化因子受体（BAFF-R）适体-siRNA递送系统，其中适体和Dicer底物siRNA（DsiRNA）部分通过“粘性桥”连接。BAFF-R在B细胞恶性肿瘤表面过度表达，使得适体-粘性-siRNA纳米颗粒能够结合并内化。STAT3 siRNA被封装在由BAFF-R适体递送的纳米颗粒中，并定位于细胞质，从而在多种B细胞系中导致STAT3 mRNA的强效基因沉默。此外，这些纳米颗粒不会诱导细胞增殖和凋亡。总体而言，适体介导的递送策略提供了一套工具，有望成为一种更广泛应用于疾病治疗的治疗方式。
