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Nanoparticles Based on Poly (β-Amino Ester) and HPV16-Targeting CRISPR/shRNA as Potential Drugs for HPV16-Related Cervical Malignancy

Authors :
Ci Ren
Peng Wu
Chun Gao
Liming Wang
Xun Tian
Junbo Hu
Wencheng Ding
Jing Cheng
Rong Liu
Zhiping Zhang
Hui Wang
Hui Shen
Lan Yu
Zheng Hu
Ding Ma
Da Zhu
Ming Deng
Ling Xi
Songwei Tan
Source :
Molecular Therapy. 26:2443-2455
Publication Year :
2018
Publisher :
Elsevier BV, 2018.

Abstract

Persistent high-risk HPV infection is the main cause of cervical cancer. The HPV oncogene E7 plays an important role in HPV carcinogenesis. Currently, HPV vaccines do not offer an effective treatment for women who already present with cervical disease, and recommended periodical cervical screenings are difficult to perform in countries and areas lacking medical resources. Our aim was to develop nanoparticles (NPs) based on poly (β-amino ester) (PBAE) and HPV16 E7-targeting CRISPR/short hairpin RNA (shRNA) to reduce the levels of HPV16 E7 as a preliminary form of a drug to treat HPV infection and its related cervical malignancy. Our NPs showed low toxicity in cells and mouse organs. By reducing the expression of HPV16 E7, our NPs could inhibit the growth of cervical cancer cells and xenograft tumors in nude mice, and they could reverse the malignant cervical epithelium phenotype in HPV16 transgenic mice. The performance of NPs containing shRNA is better than that of NPs containing CRISPR. HPV-targeting NPs consisting of PBAE and CRISPR/shRNA could potentially be developed as drugs to treat HPV infection and HPV-related cervical malignancy.

Details

ISSN :
15250016
Volume :
26
Database :
OpenAIRE
Journal :
Molecular Therapy
Accession number :
edsair.doi.dedup.....2ab835ef91749fede233f2270c390c09
Full Text :
https://doi.org/10.1016/j.ymthe.2018.07.019