持续高危HPV感染是宫颈癌发生的主要因素，为下调HPV致癌基因的表达并诱导HPV感染宫颈癌细胞的凋亡，拟构建靶向切割HPV癌基因的CRISPR/Cas9基因编辑质粒，同时考虑到单独质粒难以扩散进入细胞以及宫颈癌发生位置的特殊性，申请人引入具有黏膜粘附性的壳聚糖与阳离子聚合物聚（β-氨基酯）接枝共同递送CRISPR/Cas9质粒。将载体系统与质粒复合形成纳米粒，由于载体独特的黏膜粘附功能，经阴道局部给药后，能促进给药体系在阴道部位的滞留，进一步跨越宫颈癌细胞内外生理屏障，被肿瘤细胞摄取，通过“质子海绵效应”实现内涵体/溶酶体逃逸，释放质粒，进而特异性地切割宫颈癌细胞中的HPV致癌基因，诱导肿瘤细胞凋亡，达到降低病毒负荷、清除病毒及病变细胞、逆转癌变的目的，实现对宫颈癌的高效基因治疗。

Persistent high-risk HPV infection is the main factor for cervical cancer. CRISPR/Cas9 gene editing system is constructed to specifically cleave HPV oncogene, thus inducing the down-regulation of HPV oncogene expression and the apoptosis of cervical cancer cells. Considering the poor diffusivity of the plasmid and the part-specificity of cervical cancer, chitosan with mucosal adhesion and poly (β-amino ester) are grafted to deliver CRISPR/Cas9 plasmid. The carrier system can form composite nanoparticles with plasmid, which can promote the retention in the vaginal owing to the mucoadhesion property of the carrier after administered locally through the vagina, and improve the uptake by crossing the intracellular and intercellular barrier. Then the plasmid is released by endosome/lysosome escape through “proton sponge” effect, thus specifically cleaving HPV oncogene, inducing the apoptosis of cervical cancer cells, lowering virus load, removing virus and diseased cells, reversing the cancerous, finally achieving the effectively gene therapy of cervical cancer.