Journal Article

Therapeutic Evaluation of Epstein-Barr Virus-encoded Latent Membrane Protein-1 Targeted DNAzyme for Treating of Nasopharyngeal Carcinomas

Yang, Tubao, Liu, Xiaoyu, Yang, Lifang, Liao, Weihua, Tang, Faqing, Liao, Yuping, Fu, Jia, Tan, Guolin, He, Fengjiao, Jiang, Wenjuan, Qiu, Yuanzheng, Cao, Ya, Feng, Deyun, Zhang, Ling, Jiang, Wuzhong, Wang, Xiaoyi, Hou, Bob L, Sun, Lun-Quan

2014

Overview

The ability of the 10–23 DNAzyme to specifically cleave RNA with high efficiency has fuelled expectation that this agent may have useful applications for targeted therapy. Here, we, for the first time, investigated the antitumor and radiosensitizing effects of a DNAzyme (DZ1) targeted to the Epstein-Barr virus (EBV)-LMP1 mRNA of nasopharyngeal carcinoma (NPC) in patients. Preclinical studies indicated that the DNAzyme was safe and well tolerated. A randomized and double-blind clinical study was conducted in 40 NPC patients who received DZ1 or saline intratumorally, in conjunction with radiation therapy. Tumor regression, patient survival, EBV DNA copy number and tumor microvascular permeability were assessed in a 3-month follow-up. The mean tumor regression rate at week 12 was significantly higher in DZ1 treated group than in the saline control group. Molecular imaging analysis showed that DZ1 impacted on tumor microvascular permeability as evidenced by a faster decline of the Ktrans in DZ1-treated patients. The percentage of the samples with undetectable level of EBV DNA copy in the DZ1 group was significantly higher than that in the control group. No adverse events that could be attributed to the DZ1 injection were observed in patients.

• Publisher: Elsevier Inc,Elsevier Limited,Nature Publishing Group
• Subject: Adult / Animals / Apoptosis / Cancer / Carcinoma / Cell Line, Tumor / Disease Models, Animal / DNA, Catalytic - administration & dosage / DNA, Catalytic - adverse effects / DNA, Catalytic - genetics / DNA, Catalytic - metabolism / DNA, Viral / Epstein-Barr virus / Female / Gene Dosage / Gene Expression / Genes, Reporter / Herpesvirus 4, Human - genetics / Herpesvirus 4, Human - metabolism / Humans / Kidney Function Tests / Kinases / Liver Function Tests / Medical research / Middle Aged / Nasopharyngeal Carcinoma / Nasopharyngeal Neoplasms - genetics / Nasopharyngeal Neoplasms - therapy / Nasopharyngeal Neoplasms - virology / Original / Pathogenesis / Permeability / Plasma / Proteins / Radiation therapy / Radiotherapy, Adjuvant / Signal transduction / Treatment Outcome / Viral Matrix Proteins - genetics / Viral Matrix Proteins - metabolism / Xenograft Model Antitumor Assays