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In Vivo SELEX of an Inhibitory NSCLC-Specific RNA Aptamer from PEGylated RNA Library.
Molecular Therapy - Nucleic Acids ( IF 8.8 ) Pub Date : 2017-12-09 , DOI: 10.1016/j.omtn.2017.12.003
Hanlu Wang 1 , Yibang Zhang 2 , Haiping Yang 3 , Meng Qin 4 , Xinxin Ding 5 , Rihe Liu 6 , Yongping Jiang 4
Affiliation  

Aptamers are widely used in numerous biochemical, bioanalytical, and biological studies. Most aptamers are developed through an in vitro selection process called SELEX against either purified targets or living cells expressing targets of interest. We report here an in vivo SELEX in mice using a PEGylated RNA library for the identification of a 2′-F RNA aptamer (RA16) that specifically binds to NCI-H460 non-small-cell lung cancer cells with an affinity (KD) of 9 ± 2 nM. Interestingly, RA16 potently inhibited cancer cell proliferation in a dose-dependent manner with an IC50 of 116.7 nM. When tested in vivo in xenografted mice, RA16 showed gradual migration toward tumor and accumulation at tumor site over time. An in vivo anti-cancer study showed that the average inhibition rate for mouse tumors in the RA16-treated group was 54.26% ± 5.87% on day 16 versus the control group. The aptamer RA16 adducted with epirubicin (RA16-epirubicin) showed significantly higher toxicity against targeted NCI-H460 cells and low toxicity against non-targeted tumor cells. Furthermore, RA16-epirubicin adduct exhibited in vivo anti-cancer efficacy, with an inhibition rate of 64.38% ± 7.92% when administrated in H460 xenograft mouse model. In summary, a specific bi-functional RNA aptamer RA16 was selected targeting and inhibiting toward NCI-H460 in vitro and in vivo.



中文翻译:

PEG化RNA文库中的抑制性NSCLC特异性RNA适体的体内SELEX。

适体广泛用于许多生化,生物分析和生物学研究中。大部分的适体通过开发在VITR称为SELEX对纯化的目标或表达感兴趣的目标活细胞O选择过程。我们在这里报告了使用PEG化RNA库在小鼠体内进行SELEX鉴定2'-F RNA适体(RA16)的过程,该适体以亲和力(K D)特异性结合NCI-H460非小细胞肺癌细胞为9±2 nM。有趣的是,RA16以剂量依赖性方式有效抑制癌细胞增殖,IC 50为116.7 nM。体内测试在异种移植小鼠中,RA16随着时间的流逝逐渐向肿瘤迁移并在肿瘤部位积聚。的体内抗癌研究表明,RA16治疗组的平均抑制率小鼠肿瘤为54.26%±上比对照组16天5.87%。与表柔比星(RA16-厄比霉素)加成的适体RA16对靶向NCI-H460细胞表现出明显更高的毒性,对非靶向肿瘤细胞表现出低毒性。此外,当在H460异种移植小鼠模型中给药时,RA16-厄比霉素加合物具有体内抗癌功效,抑制率为64.38%±7.92%。综上所述,在体外体内均选择了靶向NCI-H460并抑制NCI-H460的双功能RNA适体RA16

更新日期:2017-12-09
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