Effective delivery of genome editor to cervical cancer targeting Mcl1 for cancer therapy

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 EVs<sup>RNP</sup> (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.

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Publication Details

Journal
Cancer Gene Therapy
Published
2026-01-27
DOI
https://doi.org/10.1038/s41417-025-00958-w
Primary Topic
Extracellular vesicles in disease
Type
article
Field-Weighted Citation Impact
0.00
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article

Effective delivery of genome editor to cervical cancer targeting Mcl1 for cancer therapy

Yue Wan, Xun Chen, Guannan Zhou, Shengwu Wang et al.
Cancer Gene Therapy
Extracellular vesicles in disease
article

Effective delivery of genome editor to cervical cancer targeting Mcl1 for cancer therapy

Yue Wan, Xun Chen, Guannan Zhou, Shengwu Wang, Xiaoyan Ying, Yiming He, Haiyan Zhang
article en

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 EVs<sup>RNP</sup> (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.

Cancer Gene Therapy
Second Affiliated Hospital of Nanjing Medical University (CN), Obstetrics and Gynecology Hospital of Fudan University (CN), Nanjing Jiangning Hospital (CN), Nanjing Medical University (CN)
Good health and well-being
Openalex Percentile: Top 77%
Extracellular vesicles in disease
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