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Tetrahedral Framework Nucleic Acids Loaded with Aptamer AS1411 for siRNA Delivery and Gene Silencing in Malignant Melanoma
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2021-01-26 , DOI: 10.1021/acsami.0c23005
Dexuan Xiao 1 , Yanjing Li 1 , Taoran Tian 1 , Tianxu Zhang 1 , Sirong Shi 1 , Boyao Lu 1 , Yang Gao 1 , Xin Qin 1 , Mei Zhang 1 , Wei Wei 2 , Yunfeng Lin 1, 3
Affiliation  

siRNA is found to effectively knock down the target gene in cells, which is considered a promising strategy for gene therapy. However, the application of siRNA is limited due to its low efficiency of the cellular uptake. Tetrahedral framework nucleic acids (tFNAs) are synthesized by four single-stranded DNAs and show multiple biological functions in recent studies, especially suitable for drug delivery. More than 60% of malignant melanomas are associated with Braf gene mutation, an attractive therapeutic target for RNA interference. In this study, we modified anti-Braf siRNA (siBraf) with tFNAs to downregulate the target gene. Meanwhile, we directly incorporated AS1411 (a DNA aptamer) to our nanostructure, which assists tFNAs to improve the cellular uptake efficacy of siBraf significantly. The results indicated that tFNAs-AS1411-siBraf exhibited more potent activity to cleave Braf mRNA than free siBraf. This study may provide a new idea for the combination therapy of siRNA and aptamers via DNA nanomaterials to achieve gene silencing.

中文翻译:

载有适体AS1411的四面体框架核酸,用于恶性黑色素瘤中的siRNA传递和基因沉默。

siRNA被发现可以有效地敲除细胞中的靶基因,这被认为是一种有前景的基因治疗策略。然而,由于siRNA的细胞摄取效率低,因此其应用受到限制。四面体框架核酸(tFNA)是由四个单链DNA合成的,在最近的研究中显示出多种生物学功能,特别适合于药物递送。超过60%的恶性黑色素瘤与Braf基因突变有关,Braf基因突变是RNA干扰的有吸引力的治疗靶标。在这项研究中,我们用tFNA修饰了抗Braf siRNA(siBraf),以下调靶基因。同时,我们将AS1411(DNA适体)直接掺入到我们的纳米结构中,这有助于tFNA显着提高siBraf的细胞摄取功效。结果表明,与游离siBraf相比,tFNAs-AS1411-siBraf显示出更强的切割Braf mRNA的活性。这项研究可能为通过DNA纳米材料实现siRNA与适体的联合治疗提供新的思路,以实现基因沉默。
更新日期:2021-02-10
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