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经阴道递药的 CRISPR-Cas9 技术:例如,HPV 感染的治疗。

Intravaginal delivery for CRISPR-Cas9 technology: For example, the treatment of HPV infection.

机构信息

Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Genetic Disease Diagnosis Center of Shaanxi Province, Xi'an, Shaanxi, China.

出版信息

J Med Virol. 2023 Feb;95(2):e28552. doi: 10.1002/jmv.28552.

DOI:10.1002/jmv.28552
PMID:36734062
Abstract

The increasing incidence of sexually transmitted diseases in women, including human papillomavirus (HPV) infection, has led to the need to develop user-friendly potential prevention methods. At present, although there are several therapeutic parts, none of them has a preventive effect, but they are only limited to providing patients with symptom relief. Researchers have now recognized the need to find effective local preventive agents. One of the potential undiscovered local fungicides is the vaginal delivery of CRISPR/Cas9. CRISPR/Cas9 delivery involves silencing gene expression in a sequence-specific manner in the pathogenic agent, thus showing microbicidal activity. However, vaginal mucosal barrier and physiological changes (such as pH value and variable epithelial thickness in the menstrual cycle) are the main obstacles to effective delivery and cell uptake of CRISPR/Cas9. To enhance the vaginal delivery of CRISPR/Cas9, so far, nano-carrier systems such as lipid delivery systems, macromolecular systems, polymer nanoparticles, aptamers, and cell-penetrating peptides have been extensively studied. In this paper, various nano-carriers and their prospects in the preclinical stage are described, as well as the future significance of CRISPR/Cas9 vaginal delivery based on nano-carriers.

摘要

越来越多的女性性病,包括人乳头瘤病毒(HPV)感染的发生率,已经导致需要开发用户友好的潜在预防方法。目前,尽管有几种治疗方法,但没有一种具有预防作用,而只是限于为患者提供症状缓解。研究人员现在已经认识到需要寻找有效的局部预防剂。一种潜在的未被发现的局部杀真菌剂是阴道内递送 CRISPR/Cas9。CRISPR/Cas9 的递送达是通过在病原体中以序列特异性的方式沉默基因表达,从而表现出杀菌活性。然而,阴道黏膜屏障和生理变化(如月经周期中 pH 值和可变上皮厚度)是有效递送和细胞摄取 CRISPR/Cas9 的主要障碍。为了增强 CRISPR/Cas9 的阴道递送,迄今为止,已经广泛研究了各种纳米载体系统,如脂质传递系统、大分子系统、聚合物纳米颗粒、适体和穿透细胞肽。本文描述了各种纳米载体及其在临床前阶段的前景,以及基于纳米载体的 CRISPR/Cas9 阴道递送的未来意义。

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