CRISPR/Cas9 Nanoeditor of Double Knockout Large Fragments of E6 and E7 Oncogenes for Reversing Drugs Resistance in Cervical Cancer

Overview

Journal J Nanobiotechnology

Publisher Biomed Central

Specialty Biotechnology

Date 2021 Aug 6

PMID 34353334

Citations 8

Authors

Xianhuang Li

Mingming Guo

Bei Hou

Bin Zheng

Zhiyun Wang

Mengqian Huang

Yanan Xu

Jin Chang

Tao Wang

Affiliations

Soon will be listed here.

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.

Citing Articles

Harnessing the evolving CRISPR/Cas9 for precision oncology.

Li T, Li S, Kang Y, Zhou J, Yi M J Transl Med. 2024; 22(1):749.

PMID: 39118151 PMC: 11312220. DOI: 10.1186/s12967-024-05570-4.

Designing cytochrome P450 enzymes for use in cancer gene therapy.

Carrera-Pacheco S, Mueller A, Puente-Pineda J, Zuniga-Miranda J, Guaman L Front Bioeng Biotechnol. 2024; 12:1405466.

PMID: 38860140 PMC: 11164052. DOI: 10.3389/fbioe.2024.1405466.

The Evolving Landscape of Cervical Cancer: Breakthroughs in Screening and Therapy Through Integrating Biotechnology and Artificial Intelligence.

Aswathy R, Sumathi S Mol Biotechnol. 2024; 67(3):925-941.

PMID: 38573545 DOI: 10.1007/s12033-024-01124-7.

Dexmedetomidine activates the PKA/CREB pathway and inhibits proinflammatory factor expression through β2 adrenergic receptors.

Zhang B, Shen J Immun Inflamm Dis. 2024; 12(2):e1176.

PMID: 38411331 PMC: 10898205. DOI: 10.1002/iid3.1176.

CRISPR/Cas9 systems: Delivery technologies and biomedical applications.

Du Y, Liu Y, Hu J, Peng X, Liu Z Asian J Pharm Sci. 2023; 18(6):100854.

PMID: 38089835 PMC: 10711398. DOI: 10.1016/j.ajps.2023.100854.

References

Tian B, Liu J, Liu B, Dong Y, Liu J, Song Y . p53 Suppresses lung resistance-related protein expression through Y-box binding protein 1 in the MCF-7 breast tumor cell line. J Cell Physiol. 2011; 226(12):3433-41. DOI: 10.1002/jcp.22700. View

Rabachini T, Boccardo E, Andrade R, Perez K, Nonogaki S, Midea Cuccovia I . HPV-16 E7 expression up-regulates phospholipase D activity and promotes rapamycin resistance in a pRB-dependent manner. BMC Cancer. 2018; 18(1):485. PMC: 5923196. DOI: 10.1186/s12885-018-4392-8. View

Kennedy E, Kornepati A, Goldstein M, Bogerd H, Poling B, Whisnant A . Inactivation of the human papillomavirus E6 or E7 gene in cervical carcinoma cells by using a bacterial CRISPR/Cas RNA-guided endonuclease. J Virol. 2014; 88(20):11965-72. PMC: 4178730. DOI: 10.1128/JVI.01879-14. View

Livney Y, Assaraf Y . Rationally designed nanovehicles to overcome cancer chemoresistance. Adv Drug Deliv Rev. 2013; 65(13-14):1716-30. DOI: 10.1016/j.addr.2013.08.006. View

Goodwin E, DiMaio D . Repression of human papillomavirus oncogenes in HeLa cervical carcinoma cells causes the orderly reactivation of dormant tumor suppressor pathways. Proc Natl Acad Sci U S A. 2000; 97(23):12513-8. PMC: 18795. DOI: 10.1073/pnas.97.23.12513. View

Mu P, Zhang Z, Benelli M, Karthaus W, Hoover E, Chen C . SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer. Science. 2017; 355(6320):84-88. PMC: 5247742. DOI: 10.1126/science.aah4307. View

Meuwissen R, Linn S, Linnoila R, Zevenhoven J, Mooi W, Berns A . Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model. Cancer Cell. 2003; 4(3):181-9. DOI: 10.1016/s1535-6108(03)00220-4. View

Martinez-Lage M, Torres-Ruiz R, Puig-Serra P, Moreno-Gaona P, Martin M, Moya F . In vivo CRISPR/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells. Nat Commun. 2020; 11(1):5060. PMC: 7544871. DOI: 10.1038/s41467-020-18875-x. View

Sultana H, Kigawa J, Kanamori Y, Itamochi H, Oishi T, Sato S . Chemosensitivity and p53-Bax pathway-mediated apoptosis in patients with uterine cervical cancer. Ann Oncol. 2003; 14(2):214-9. DOI: 10.1093/annonc/mdg071. View

10.

Ebos J . Prodding the Beast: Assessing the Impact of Treatment-Induced Metastasis. Cancer Res. 2015; 75(17):3427-35. DOI: 10.1158/0008-5472.CAN-15-0308. View

11.

Cao X, Hou J, An Q, Assaraf Y, Wang X . Towards the overcoming of anticancer drug resistance mediated by p53 mutations. Drug Resist Updat. 2019; 49:100671. DOI: 10.1016/j.drup.2019.100671. View

12.

Kampan N, Madondo M, McNally O, Quinn M, Plebanski M . Paclitaxel and Its Evolving Role in the Management of Ovarian Cancer. Biomed Res Int. 2015; 2015:413076. PMC: 4475536. DOI: 10.1155/2015/413076. View

13.

Meisel J, Gokel G . A Simplified Direct Lipid Mixing Lipoplex Preparation: Comparison of Liposomal-, Dimethylsulfoxide-, and Ethanol-Based Methods. Sci Rep. 2016; 6:27662. PMC: 4914933. DOI: 10.1038/srep27662. View

14.

Schmidt M, Bachhuber A, Victor A, Steiner E, Mahlke M, Lehr H . p53 expression and resistance against paclitaxel in patients with metastatic breast cancer. J Cancer Res Clin Oncol. 2003; 129(5):295-302. DOI: 10.1007/s00432-003-0430-1. View

15.

DiPaolo J, Alvarez-Salas L . Advances in the development of therapeutic nucleic acids against cervical cancer. Expert Opin Biol Ther. 2004; 4(8):1251-64. DOI: 10.1517/14712598.4.8.1251. View

16.

Vasan N, Baselga J, Hyman D . A view on drug resistance in cancer. Nature. 2019; 575(7782):299-309. PMC: 8008476. DOI: 10.1038/s41586-019-1730-1. View

17.

Zhu S, Yung B, Chandra S, Niu G, Antaris A, Chen X . Near-Infrared-II (NIR-II) Bioimaging Off-Peak NIR-I Fluorescence Emission. Theranostics. 2018; 8(15):4141-4151. PMC: 6096392. DOI: 10.7150/thno.27995. View

18.

Marangolo M, Bengala C, Conte P, Danova M, Pronzato P, Rosti G . Dose and outcome: the hurdle of neutropenia (Review). Oncol Rep. 2006; 16(2):233-48. View

19.

Mashouri L, Yousefi H, Aref A, Ahadi A, Molaei F, Alahari S . Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Mol Cancer. 2019; 18(1):75. PMC: 6444571. DOI: 10.1186/s12943-019-0991-5. View

20.

Du B, Shim J . Targeting Epithelial-Mesenchymal Transition (EMT) to Overcome Drug Resistance in Cancer. Molecules. 2016; 21(7). PMC: 6273543. DOI: 10.3390/molecules21070965. View