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Human Papillomavirus Oncogene Manipulation Using Clustered Regularly Interspersed Short Palindromic Repeats/Cas9
Shuai Zhen1,2, Yan Liu3, Jiaojiao Lu1
1Center for Translational Medicine, Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R China.
Abstract:
Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) technology enables targeted gene editing, but cancer gene therapy with this approach requires improvements to enable safe and efficient delivery of CRISPR/Cas9 to tumors. We developed and evaluated a self-assembled liposome to selectively deliver CRISPR/Cas9 to cancer tissues. Our CRISPR/Cas9 system effectively inhibited proliferation of human papillomavirus (HPV) 16-positive cervical cancer cells and induced apoptosis by inactivating the HR-HPV16E6/E7 oncogene. Based on this system, we prepared a long-circulating pH-sensitive cationic nano-liposome complex with a high cell targeting and gene knockout rate. Intratumoral injection of cationic liposomes targeted to splicing HPV16 E6/E7 in nude mice significantly inhibited tumor growth without significant toxicity in vivo. Liposomes that targeted HPV16 E6/E7 splicing were established as a basis for treatment of HPV16-positive cervical cancer drug candidates. Our study demonstrates that this liposome offers an efficient delivery system for nonviral gene editing, adding to the armamentarium of gene editing tools to advance safe and effective precision medicine-based cancer therapeutics.
Insights
Researchers developed a novel liposome delivery system for CRISPR/Cas9 gene editing to target and treat HPV16-positive cervical cancer. This targeted approach effectively inhibited tumor growth and induced apoptosis with minimal toxicity.
Area of Science:
- Biomedical Engineering
- Oncology
- Gene Therapy
Background:
- Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) technology offers targeted gene editing capabilities.
- Effective and safe delivery of CRISPR/Cas9 systems to tumors remains a challenge for cancer gene therapy.
Purpose of the Study:
- To develop and evaluate a self-assembled liposome for selective delivery of CRISPR/Cas9 to cancer tissues.
- To assess the efficacy of the liposome-CRISPR/Cas9 system in treating human papillomavirus (HPV) 16-positive cervical cancer.
Main Methods:
- Development of a pH-sensitive cationic nano-liposome complex for CRISPR/Cas9 delivery.
- Evaluation of the system's ability to target and inactivate the HR-HPV16E6/E7 oncogene in cervical cancer cells.
- Intratumoral injection of the liposome complex in nude mice models to assess tumor inhibition and toxicity.
Main Results:
- The CRISPR/Cas9 liposome system effectively inhibited proliferation and induced apoptosis in HPV 16-positive cervical cancer cells by inactivating the HR-HPV16E6/E7 oncogene.
- The nano-liposome complex demonstrated high cell targeting and gene knockout efficiency.
- Intratumoral administration in mice significantly inhibited tumor growth with no significant observed toxicity.
Conclusions:
- The developed liposome serves as an efficient nonviral delivery system for gene editing applications.
- This technology provides a promising basis for developing drug candidates for HPV16-positive cervical cancer treatment.
- The study advances precision medicine-based cancer therapeutics through safe and effective gene editing delivery.
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