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Delivery of genome editing tools: A promising strategy for HPV-related cervical malignancy therapy.
Expert Opinion on Drug Delivery ( IF 6.6 ) Pub Date : 2020-04-13 , DOI: 10.1080/17425247.2020.1747429
Shahin Aghamiri 1, 2 , Sam Talaei 3 , Soheil Roshanzamiri 4 , Farshid Zandsalimi 5 , Elnaz Fazeli 6 , Mansur Aliyu 7 , Omid Kheiry Avarvand 8 , Zahra Ebrahimi 9 , Mahsa Keshavarz-Fathi 10, 11 , Hossein Ghanbarian 2, 9, 12
Affiliation  

Introduction

Persistent high-risk human papillomavirus infection is the main cause of various types of cancer especially cervical cancer. The E6 and E7 oncoproteins of HPV play critical roles in promoting carcinogenesis and cancer cell growth. As a result, E6 and E7 oncogenes are considered as promising therapeutic targets for cervical cancer. Recently, the development of genome-editing technologies including transcription activator-like effector nucleases (TALEN), meganucleases (MNs), zinc finger nucleases (ZFN), and more importantly clustered regularly interspaced short palindromic repeat-CRISPR-associated protein (CRISPR-Cas) has sparked a revolution in the cervical cancer-targeted therapy. However, due to immunogenicity, off-target effect, renal clearance, guide RNA (gRNA) nuclease degradation, and difficult direct transportation into the cytoplasm and nucleus, the safe and effective delivery is considered as the Achilles’ heel of this robust strategy.

Areas covered

In this review, we discuss cutting-edge available strategies for in vivo delivery of genome-editing technologies for HPV-induced cervical cancer therapy. Moreover, the combination of genome-editing tools and other therapies has been fully discussed.

Expert opinion

The combination of nanoparticle-based delivery systems and genome-editing tools is a promising powerful strategy for cervical cancer therapy. The most significant limitations of this strategy that need to be focused on are low efficiency and off-target events.



中文翻译:

提供基因组编辑工具:HPV相关宫颈恶性肿瘤治疗的一种有前途的策略。

介绍

持续的高危人类乳头瘤病毒感染是各种类型的癌症,尤其是宫颈癌的主要原因。HPV的E6和E7癌蛋白在促进癌变和癌细胞生长中起关键作用。结果,E6和E7癌基因被认为是宫颈癌的有希望的治疗靶标。最近,基因组编辑技术的发展,包括转录激活因子样效应子核酸酶(TALEN),大范围核酸酶(MNs),锌指核酸酶(ZFN),更重要的是聚簇成规则间隔的短回文重复序列-CRISPR-相关蛋白(CRISPR-Cas )引发了针对宫颈癌的疗法的革命。但是,由于具有免疫原性,脱靶效应,肾清除率,指导RNA(gRNA)核酸酶降解,

覆盖区域

在这篇综述中,我们讨论了用于HPV诱导的宫颈癌治疗的基因组编辑技术的体内递送的前沿可用策略。而且,已经充分讨论了基因组编辑工具和其他疗法的组合。

专家意见

基于纳米颗粒的递送系统和基因组编辑工具的结合是宫颈癌治疗的有前途的有力策略。该策略需要重点关注的最主要限制是低效率和脱靶事件。

更新日期:2020-04-13
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