Fakhoury Johans J, McLaughlin Christopher K, Edwardson Thomas W, Conway Justin W, Sleiman Hanadi F
Department of Chemistry and Center for Self-Assembled Chemical Structures, McGill University , 801 Sherbrooke Street West, Montreal, Quebec H3A 0B8, Canada.
Biomacromolecules. 2014 Jan 13;15(1):276-82. doi: 10.1021/bm401532n. Epub 2013 Dec 26.
RNA interference (RNAi) is a powerful therapeutic strategy that induces gene silencing by targeting disease-causing mRNA and can lead to their removal through degradation pathways. The potential of RNAi is especially relevant in cancer therapy, as it can be designed to regulate the expression of genes involved in all stages of tumor development (initiation, growth, and metastasis). We have generated gene silencing 3D DNA prisms that integrate antisense oligonucleotide therapeutics at 1, 2, 4, and 6 positions. Synthesis of these structures is readily achieved and leads to the assembly of highly monodisperse and well-characterized structures. We have shown that antisense strands scaffolded on DNA cages can readily induce gene silencing in mammalian cells and maintain gene knockdown levels more effectively than single and double stranded controls through increased stability of bound antisense units.
RNA干扰（RNAi）是一种强大的治疗策略，它通过靶向致病mRNA诱导基因沉默，并可通过降解途径导致其清除。RNAi的潜力在癌症治疗中尤为重要，因为它可以被设计用来调节参与肿瘤发展各个阶段（起始、生长和转移）的基因表达。我们已经生成了基因沉默的3D DNA棱镜，其在1、2、4和6位整合了反义寡核苷酸疗法。这些结构的合成很容易实现，并导致高度单分散且特征明确的结构的组装。我们已经表明，构建在DNA笼上的反义链能够在哺乳动物细胞中轻易诱导基因沉默，并且通过增加结合反义单元的稳定性，比单链和双链对照更有效地维持基因敲低水平。
