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CRISPR/Cas9 纳米编辑技术双敲除 E6 和 E7 癌基因大片段逆转宫颈癌耐药性

CRISPR/Cas9 nanoeditor of double knockout large fragments of E6 and E7 oncogenes for reversing drugs resistance in cervical cancer.

机构信息

School of Life Sciences, Tianjin University, 92 Weijin Road, Nankai, 300072, Tianjin, China.

Academy of Medical Engineering and Translational Medicine, Tianjin Key Laboratory of Brain Science and Neural Engineering, Xincheng Hospital of Tianjin University, Tianjin University, 92 Weijin Road, Nankai, 300072, Tianjin, China.

出版信息

J Nanobiotechnology. 2021 Aug 5;19(1):231. doi: 10.1186/s12951-021-00970-w.

DOI:10.1186/s12951-021-00970-w
PMID:34353334
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8340365/
Abstract

Drug resistance of tumor cells is always a headache problem in clinical treatment. In order to combat chemotherapy-resistance in cervical cancer and improve treatment effect, we design a CRISPR/Cas9 nanoeditor to knock out two key oncogenes E6 and E7 that lead to drug tolerance. Meanwhile, the deletion of these two oncogenes can effectively reactivate p53 and pRB signaling pathways that inhibit the growth of tumor cells. Our results demonstrated the nanoeditor could simultaneously delete two oncogenes, and the size of DNA fragments knocked out reaches an unprecedented 563 bp. After the preparation of cationic liposomes combined with chemotherapy drug docetaxel (DOC), this nanosystem can significantly inhibit the drug tolerance of cancer cells and improve the therapeutic effect of cervical cancer. Therefore, this study provides a promising strategy for the treatment of cervical cancer by combining chemotherapy and double-target gene therapy. This strategy can also be applied in other disease models to customize personalized anti-tumor strategies by simply changing chemotherapy drugs and targeted genes.

摘要

肿瘤细胞的耐药性一直是临床治疗中的一个令人头疼的问题。为了对抗宫颈癌的化疗耐药性，提高治疗效果，我们设计了一种 CRISPR/Cas9 纳米编辑器来敲除导致药物耐受的两个关键癌基因 E6 和 E7。同时，这两个癌基因的缺失可以有效重新激活抑制肿瘤细胞生长的 p53 和 pRB 信号通路。我们的结果表明，纳米编辑器可以同时敲除两个癌基因，敲除的 DNA 片段大小达到前所未有的 563bp。制备阳离子脂质体并与化疗药物多西紫杉醇（DOC）结合后，该纳米系统可以显著抑制癌细胞的耐药性，提高宫颈癌的治疗效果。因此，本研究通过联合化疗和双靶基因治疗为宫颈癌的治疗提供了一种有前景的策略。通过简单改变化疗药物和靶向基因，该策略还可以应用于其他疾病模型，制定个性化的抗肿瘤策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6470/8340365/25754ea37bb6/12951_2021_970_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6470/8340365/b10b9a5460e0/12951_2021_970_Figa_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6470/8340365/bdf9aab63b72/12951_2021_970_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6470/8340365/763ff7b14287/12951_2021_970_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6470/8340365/72dde163b509/12951_2021_970_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6470/8340365/265401a6008f/12951_2021_970_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6470/8340365/d8ea72f132aa/12951_2021_970_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6470/8340365/67f082383d54/12951_2021_970_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6470/8340365/25754ea37bb6/12951_2021_970_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6470/8340365/b10b9a5460e0/12951_2021_970_Figa_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6470/8340365/bdf9aab63b72/12951_2021_970_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6470/8340365/763ff7b14287/12951_2021_970_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6470/8340365/72dde163b509/12951_2021_970_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6470/8340365/265401a6008f/12951_2021_970_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6470/8340365/d8ea72f132aa/12951_2021_970_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6470/8340365/67f082383d54/12951_2021_970_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6470/8340365/25754ea37bb6/12951_2021_970_Fig7_HTML.jpg

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