State Key Laboratory of Elemento-Organic Chemistry, Department of Chemical Biology, National Pesticide Engineering Research Center, Collaborative Innovation Center of Chemical Science and Engineering, College of Chemistry, Nankai University, Tianjin 300071, China.
Molecules. 2022 Oct 16;27(20):6943. doi: 10.3390/molecules27206943.
Multiple proteins are involved in network regulation through the crosstalk of different signaling pathways in cancers. Here, we propose a novel strategy of genome therapy with branch-PCR-assembled gene nanovectors to perform network-based gene regulation at multiple levels for cancer therapy. To validate network-based multiplex-gene regulation for genome therapy, we chose to simultaneously target one tumor suppressor gene () and one oncogene () in two different signaling pathways. The results showed that, compared to gene nanovectors targeting single genes (NP-TP53 and NP-shMYC), branch-PCR-assembled gene nanovectors simultaneously expressing p53 proteins and MYC shRNA arrays (NP-TP53-shMYC) showed enhanced antitumor efficacy in both MDA-MB-231 cancer cells and an MDA-MB-231-tumor-bearing mouse model. These findings indicate the feasibility and effectiveness of genome therapy in cancer therapy.
多种蛋白质通过不同信号通路在癌症中的串扰参与网络调节。在这里，我们提出了一种利用分支 PCR 组装基因纳米载体进行基于网络的多层次基因调控以进行癌症治疗的基因组治疗新策略。为了验证基于网络的多重基因调控用于基因组治疗，我们选择同时针对两个不同信号通路中的一个肿瘤抑制基因 () 和一个癌基因 ()。结果表明，与靶向单个基因的基因纳米载体（NP-TP53 和 NP-shMYC）相比，同时表达 p53 蛋白和 MYC shRNA 阵列的分支 PCR 组装基因纳米载体（NP-TP53-shMYC）在 MDA-MB-231 癌细胞和 MDA-MB-231 荷瘤小鼠模型中均显示出增强的抗肿瘤功效。这些发现表明基因组治疗在癌症治疗中的可行性和有效性。
