DNA Nanorobot Delivers Antisense Oligonucleotides Silencing c-Met Gene Expression for Cancer Therapy

DNA Nanorobot Delivers Antisense Oligonucleotides Silencing c-Met Gene Expression for Cancer Therapy
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DNA 纳米机器人提供反义寡核苷酸沉默 c-Met 基因表达用于癌症治疗

DOI:
10.1166/jbn.2019.2828
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发表时间:
2019
影响因子:
2.9
通讯作者:
Cai Xiaoxiao
Cai Xiaoxiao
中科院分区:
工程技术3区
文献类型:
--
作者:
Zhang Xiaolin;Liu Nanxin;Zhou Mi;Zhang Tao;Tian Taoran;Li Songhang;Tang Zisheng;Lin Yunfeng;Cai Xiaoxiao

文献摘要

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反义寡核苷酸因其高度的特异性和最小的副作用而被认为是一种很有前途的癌症治疗策略。它们可以特异性地与mRNA结合,沉默靶基因的表达。然而,单链DNA不能大量进入细胞,这限制了它的应用。四面体骨架核酸(TFNA)因其可编辑性和生物相容性而被认为是最理想的纳米药物载体。最重要的是,它们可以用功能分子进行修饰。C-Met的过度表达与多种肿瘤的发生、发展、耐药及预后密切相关。HGF/c-Met信号通路的激活可促进肿瘤细胞的迁移和侵袭。因此,阻断c-Met的表达是一种有效的肿瘤治疗技术。在本研究中,我们以tFNA为载体,将能与c-Met mRNA高度特异性和亲和力结合的反义寡核苷酸导入细胞内,从而抑制c-Met的表达,用于肿瘤治疗。
Antisense oligonucleotides are considered to be a promising strategy for cancer therapy because of their high specificity and minimal side effects. They can bind specifically to mRNA silencing the expression of target genes. However, ssDNA cannot enter cells in large quantities, which limits its applications. Tetrahedral framework nucleic acids (tFNA) are considered to be optimal nanoscopic drug carriers because of their editability and biocompatibility. Most importantly, they can be modified with functional molecules. The over-expression of c-Met is associated with a wide variety of tumor occurrences, developments, drug resistance and prognoses. Activation of HGF/c-Met signaling pathways can promote cell migration and invasion in cancer. Therefore, blocking the expression of c-Met is a valid technique for cancer therapy. In this study, we used tFNA as carriers to deliver antisense oligonucleotides, which can bind to c-Met mRNA with high specificity and affinity, into cells resulting in the inhibition of c-Met expression for cancer therapy.