NF-κB 是一个很有前景的癌症治疗靶点，因为它在几乎所有癌症中都过度激活，但无数的 NF-κB 抑制剂由于副作用很少成为临床药物。与旨在抑制 NF-κB 活性的传统癌症治疗相反，本研究开发了一种名为 HOPE 的新方法，该方法侧重于激活癌细胞内的外源效应基因 CRISPR-Cas13a，这是通过利用先前的 NF-κB 特异性启动子 DMP 来实现的构建，然后在 mRNA 水平上靶向并抑制癌基因 TERT、PLK1、KRAS 和 MYC 的表达。我们评估了HOPE在各种培养细胞中的抗肿瘤作用，并证实它可以明显诱导癌细胞死亡而不影响正常细胞。通过将HOPE包装成腺相关病毒（AAV）并静脉注射来治疗皮下移植结直肠癌的小鼠。这验证了rAAV-HOPE可以显着抑制肿瘤生长且无副作用。根据scRNA-seq数据，我们观察到HOPE可以激活免疫系统并降低癌​​细胞的比例，特别是降低癌细胞的干性。这项研究阐明了 HOPE 在体外和体内抑制癌细胞生长的重要作用，此外还为癌症基因治疗提供了一种新颖的治疗技术。© 2024。作者。

NF-κB is a promising target for cancer treatment because of its overactivation in almost all cancers but countless NF-κB inhibitors rarely became clinical drugs due to side effects. In contrast to traditional cancer treatments aimed at inhibiting NF-κB activity, this study develop a novel approach termed HOPE, which focuses on activating the exogenous effector gene CRISPR-Cas13a within cancer cells, achieved by utilizing the NF-κB-specific promoter DMP previously constructed, then targets and suppresses the expression of oncogenes TERT, PLK1, KRAS and MYC at mRNA level. We evaluated the antitumour effects of HOPE in various cultured cells and confirmed it could induce obvious the death of cancer cells without affecting normal cells. By packaging HOPE into adeno-associated virus (AAV) and intravenously injected it to treat mice that were subcutaneously transplanted with colorectal cancer. This validated that rAAV-HOPE could significantly inhibit tumour growth without side effects. Based on the scRNA-seq data, we observed that HOPE could activate the immune system and decrease the proportion of cancer cells, particularly reducing the stemness of cancer cells. This study elucidates an important role of HOPE in inhibiting cancer cell growth both in vitro and in vivo, additionally provides a novel therapeutic technology for cancer gene therapy.© 2024. The Author(s).