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Published on: December 26, 2016
Effective delivery of genome editor to cervical cancer targeting Mcl1 for cancer therapy
Yue Wan1, Yiming He2, Xun Chen1
1Department of Gynecology, Sir Run Run Hospital, Nanjing Medical University, Long Mian Avenue 109 Jiangning, Nanjing, Jiangsu, China.
Abstract:
CRISPR/Cas9 represents a transformative advancement in precision therapies, offering the promise of more effective and targeted treatment options. However, there are still limitations (including off-target editing as well as unsatisfied delivery tool) which obstruct the wide application of CRISPR/Cas9. Here, an endogenic artificial extracellular vesicles (EVs) system is engineered for effective delivery of Cas9 ribonucleoprotein (RNP). We demonstrated that the endogenic Cas9 RNP were sorted by the Lamp2b and delivered by the artificial EVs, which could markedly inhibit the growth of cervical cancer cells by inducing cell apoptosis. Moreover, artificial endogenic EVsRNP (Cas9-Mcl1) could result in remarkable antitumor effects in animal models of cervical cancer through suppressing Mcl1 expression. Our findings indicate that the artificial EVs delivery strategy could deliver Cas9 RNP effectively to inhibit cancer progression, which might be a promising treatment.
Insights
This study engineered artificial extracellular vesicles (EVs) to deliver CRISPR/Cas9 gene editing tools, effectively inhibiting cervical cancer growth and progression in preclinical models.
Area of Science:
- Biotechnology
- Gene Editing
- Cancer Therapy
Background:
- CRISPR/Cas9 technology offers precision therapy potential but faces delivery and off-target editing challenges.
- Effective delivery systems are crucial for expanding CRISPR/Cas9 applications in cancer treatment.
Purpose of the Study:
- To engineer an endogenous artificial extracellular vesicle (EV) system for efficient delivery of Cas9 ribonucleoprotein (RNP).
- To evaluate the therapeutic efficacy of EV-delivered Cas9 RNP in inhibiting cervical cancer progression.
Main Methods:
- Engineered artificial EVs for endogenous Cas9 RNP sorting and delivery via Lamp2b.
- Assessed the impact of EV-delivered Cas9 RNP on cervical cancer cell growth and apoptosis in vitro.
- Evaluated the antitumor effects of artificial endogenic EVs (Cas9-Mcl1) in animal models of cervical cancer.
Main Results:
- Demonstrated successful sorting and delivery of Cas9 RNP by engineered artificial EVs.
- Observed significant inhibition of cervical cancer cell growth through induced apoptosis.
- Achieved remarkable antitumor effects in vivo by suppressing Mcl1 expression using artificial endogenic EVs.
Conclusions:
- Artificial EVs provide an effective delivery strategy for Cas9 RNP, overcoming current limitations.
- This EV-based delivery system shows promise for inhibiting cancer progression and warrants further investigation as a novel therapeutic approach.
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