E7-Targeted Nanotherapeutics for Key HPV Afflicted Cervical Lesions by Employing CRISPR/Cas9 and Poly (Beta-Amino Ester).
E7-Targeted Nanotherapeutics for Key HPV Afflicted Cervical Lesions by Employing CRISPR/Cas9 and Poly (Beta-Amino Ester).
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利用 CRISPR/Cas9 和聚（β-氨基酯）针对 E7 靶向纳米疗法治疗受 HPV 影响的关键宫颈病变。
DOI：
10.2147/ijn.s335277
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发表时间：
2021
影响因子：
8
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Xiong J;Tan S;Yu L;Shen H;Qu S;Zhang C;Ren C;Zhu D;Wang H
持续性高危型人乳头瘤病毒（HR - HPV）感染是宫颈癌的主要病因。HPV致癌基因E7在HPV致瘤过程中起关键作用。目前，HPV预防性疫苗对已患有宫颈疾病的患者无效，而且在医疗资源匮乏的国家和地区，实施推荐的常规宫颈筛查也很困难。因此，患者需要药物来治疗现有的HPV感染，从而阻断宫颈疾病的进展。
在本研究中，我们开发了由非病毒载体PBAE546和一种靶向HPV16 E7的CRISPR/Cas9重组质粒组成的纳米颗粒（NPs），作为一种针对HPV感染及相关宫颈恶性肿瘤的阴道用药。
我们的纳米颗粒在体外（细胞系活力）和体内（小鼠的各种重要器官）均显示出低毒性和高生物安全性。我们的纳米颗粒显著抑制了源自宫颈癌细胞系的异种移植瘤在裸鼠体内的生长，并显著逆转了HPV16转基因小鼠的宫颈上皮恶性表型。
我们的纳米颗粒极有潜力被开发为一种用于治疗HPV相关宫颈癌及癌前病变的药物。
Persistent HR-HPV (high-risk human papillomavirus) infection is the main cause of cervical cancer. The HPV oncogene E7 plays a key role in HPV tumorigenesis. At present, HPV preventive vaccines are not effective for patients who already have a cervical disease, and implementation of the recommended regular cervical screening is difficult in countries and regions lacking medical resources. Therefore, patients need medications to treat existing HPV infections and thus block the progression of cervical disease. In this study, we developed nanoparticles (NPs) composed of the non-viral vector PBAE546 and a CRISPR/Cas9 recombinant plasmid targeting HPV16 E7 as a vaginal treatment for HPV infection and related cervical malignancies. Our NPs showed low toxicity and high biological safety both in vitro (cell line viability) and in vivo (various important organs of mice). Our NPs significantly inhibited the growth of xenograft tumors derived from cervical cancer cell lines in nude mice and significantly reversed the cervical epithelial malignant phenotype of HPV16 transgenic mice. Our NPs have great potential to be developed as a drug for the treatment of HPV-related cervical cancer and precancerous lesions.