The anti-tumor efficacy of a recombinant oncolytic herpes simplex virus mediated CRISPR/Cas9 delivery targeting in HPV16-positive cervical cancer.

Autor: Hu Z; School of Pharmacy, Yantai University, Yantai, 264005, Shandong, China., Liu W; School of Pharmacy, Yantai University, Yantai, 264005, Shandong, China., Liu J; Beijing WellGene Company, Ltd, Beijing, 100085, China., Zhou H; Beijing WellGene Company, Ltd, Beijing, 100085, China., Sun C; Beijing WellGene Company, Ltd, Beijing, 100085, China., ChaoTian; Beijing WellGene Company, Ltd, Beijing, 100085, China., Guo X; School of Pharmacy, Yantai University, Yantai, 264005, Shandong, China., Zhu C; School of Pharmacy, Yantai University, Yantai, 264005, Shandong, China., Shao M; School of Pharmacy, Yantai University, Yantai, 264005, Shandong, China., Wang S; School of Pharmacy, Yantai University, Yantai, 264005, Shandong, China., Wei L; School of Pharmacy, Yantai University, Yantai, 264005, Shandong, China., Liu M; School of Pharmacy, Yantai University, Yantai, 264005, Shandong, China., Li S; School of Pharmacy, Yantai University, Yantai, 264005, Shandong, China., Wang J; School of Pharmacy, Yantai University, Yantai, 264005, Shandong, China., Xu H; School of Pharmacy, Yantai University, Yantai, 264005, Shandong, China., Zhu W; School of Pharmacy, Yantai University, Yantai, 264005, Shandong, China., Li X; School of Pharmacy, Yantai University, Yantai, 264005, Shandong, China; Beijing WellGene Company, Ltd, Beijing, 100085, China. Electronic address: patricklee@genevec.com., Li J; School of Pharmacy, Yantai University, Yantai, 264005, Shandong, China. Electronic address: jfli@genevec.com.
Jazyk: angličtina
Zdroj: Antiviral research [Antiviral Res] 2024 Dec; Vol. 232, pp. 106035. Date of Electronic Publication: 2024 Nov 12.
DOI: 10.1016/j.antiviral.2024.106035
Abstrakt: Cervical cancer, often driven by high-risk human papillomavirus (HPV) infections such as HPV16 or HPV18, remains a leading cause of cancer-related deaths. HPV16, found in about 90% of cervical cancer patients, harbors key oncogenic related genes (E6, E7, E2, E5) and an upstream regulatory region (URR) that contribute to cancer progression. This study introduces a novel approach using a recombinant oncolytic herpes simplex virus type 1 (HSV-1) named SONC103, armed with a CRISPR/Cas9 gene editing system. The aim was to target and disrupt integrated HPV16 genes in cervical cancer cells. Results demonstrated SONC103's capability to specifically and effectively knock down HPV16 oncogenes, thereby reducing cell proliferation and promoting apoptosis. Analyses further revealed loss of HPV16 DNA probes in infected cells' chromosomes, significant regulation of cellular processes related to tumor apoptosis, and downregulation of E6/E7 oncoproteins while increasing tumor suppressor proteins P53 and pRB. Notably, SONC103 exhibited substantial inhibition of tumor growth in a murine xenograft cervical cancer model. This study showcases the potential of the recombinant oncolytic HSV-1 virus (SONC103) in combating HPV16-positive cervical cancer by targeting oncogenes and facilitating oncolysis.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:All the authors have no conflicts of interest to declare.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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