Ionizable lipid-assisted efficient hepatic delivery of gene editing elements for oncotherapy
CRISPR/Cas9-based gene editing has emerged as a powerful biotechnological tool, that relies on Cas9 protein and single guided RNA (sgRNA) to edit target DNA. However, the lack of safe and efficient delivery carrier is one of the crucial factors restricting its clinical transformation. Here, we repor...
Guardado en:
| Autores principales: | , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
KeAi Communications Co., Ltd.
2022
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/6d004e3692a447fa8672c0d2cf7c8d45 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:6d004e3692a447fa8672c0d2cf7c8d45 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:6d004e3692a447fa8672c0d2cf7c8d452021-11-14T04:34:46ZIonizable lipid-assisted efficient hepatic delivery of gene editing elements for oncotherapy2452-199X10.1016/j.bioactmat.2021.05.051https://doaj.org/article/6d004e3692a447fa8672c0d2cf7c8d452022-03-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2452199X21002723https://doaj.org/toc/2452-199XCRISPR/Cas9-based gene editing has emerged as a powerful biotechnological tool, that relies on Cas9 protein and single guided RNA (sgRNA) to edit target DNA. However, the lack of safe and efficient delivery carrier is one of the crucial factors restricting its clinical transformation. Here, we report an ionizable lipid nanoparticle (iLP181, pKa = 6.43) based on iLY1809 lipid enabling robust gene editing in vitro and in vivo. The iLP181 effectively encapsulate psgPLK1, the best-performing plasmid expressing for both Cas9 protein and sgRNA targeting Polo-like kinase 1 (PLK1). The iLP181/psgPLK1 nanoformulation showed uniformity in size, regular nanostructure and nearly neutral zeta potential at pH 7.4. The nanoformulation effectively triggered editing of PLK1 gene with more than 30% efficiency in HepG2-Luc cells. iLP181/psgPLK1 significantly accumulated in the tumor for more than 5 days after a single intravenous injection. In addition, it also achieved excellent tumor growth suppression compared to other nucleic acid modalities such as siRNA, without inducing adverse effects to the main organs including the liver and kidneys. This study not only provides a clinically-applicable lipid nanocarrier for delivering CRISPR/Cas system (even other bioactive molecules), but also constitutes a potential cancer treatment regimen base on DNA editing of oncogenes.Chunhui LiTongren YangYuhua WengMengjie ZhangDeyao ZhaoShuai GuoBo HuWanxuan ShaoXiaoxia WangAbid HussainXing-Jie LiangYuanyu HuangKeAi Communications Co., Ltd.articleCRISPR/CasGene editingLipid nanoparticlePLK1Cancer therapyMaterials of engineering and construction. Mechanics of materialsTA401-492Biology (General)QH301-705.5ENBioactive Materials, Vol 9, Iss , Pp 590-601 (2022) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
CRISPR/Cas Gene editing Lipid nanoparticle PLK1 Cancer therapy Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5 |
| spellingShingle |
CRISPR/Cas Gene editing Lipid nanoparticle PLK1 Cancer therapy Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5 Chunhui Li Tongren Yang Yuhua Weng Mengjie Zhang Deyao Zhao Shuai Guo Bo Hu Wanxuan Shao Xiaoxia Wang Abid Hussain Xing-Jie Liang Yuanyu Huang Ionizable lipid-assisted efficient hepatic delivery of gene editing elements for oncotherapy |
| description |
CRISPR/Cas9-based gene editing has emerged as a powerful biotechnological tool, that relies on Cas9 protein and single guided RNA (sgRNA) to edit target DNA. However, the lack of safe and efficient delivery carrier is one of the crucial factors restricting its clinical transformation. Here, we report an ionizable lipid nanoparticle (iLP181, pKa = 6.43) based on iLY1809 lipid enabling robust gene editing in vitro and in vivo. The iLP181 effectively encapsulate psgPLK1, the best-performing plasmid expressing for both Cas9 protein and sgRNA targeting Polo-like kinase 1 (PLK1). The iLP181/psgPLK1 nanoformulation showed uniformity in size, regular nanostructure and nearly neutral zeta potential at pH 7.4. The nanoformulation effectively triggered editing of PLK1 gene with more than 30% efficiency in HepG2-Luc cells. iLP181/psgPLK1 significantly accumulated in the tumor for more than 5 days after a single intravenous injection. In addition, it also achieved excellent tumor growth suppression compared to other nucleic acid modalities such as siRNA, without inducing adverse effects to the main organs including the liver and kidneys. This study not only provides a clinically-applicable lipid nanocarrier for delivering CRISPR/Cas system (even other bioactive molecules), but also constitutes a potential cancer treatment regimen base on DNA editing of oncogenes. |
| format |
article |
| author |
Chunhui Li Tongren Yang Yuhua Weng Mengjie Zhang Deyao Zhao Shuai Guo Bo Hu Wanxuan Shao Xiaoxia Wang Abid Hussain Xing-Jie Liang Yuanyu Huang |
| author_facet |
Chunhui Li Tongren Yang Yuhua Weng Mengjie Zhang Deyao Zhao Shuai Guo Bo Hu Wanxuan Shao Xiaoxia Wang Abid Hussain Xing-Jie Liang Yuanyu Huang |
| author_sort |
Chunhui Li |
| title |
Ionizable lipid-assisted efficient hepatic delivery of gene editing elements for oncotherapy |
| title_short |
Ionizable lipid-assisted efficient hepatic delivery of gene editing elements for oncotherapy |
| title_full |
Ionizable lipid-assisted efficient hepatic delivery of gene editing elements for oncotherapy |
| title_fullStr |
Ionizable lipid-assisted efficient hepatic delivery of gene editing elements for oncotherapy |
| title_full_unstemmed |
Ionizable lipid-assisted efficient hepatic delivery of gene editing elements for oncotherapy |
| title_sort |
ionizable lipid-assisted efficient hepatic delivery of gene editing elements for oncotherapy |
| publisher |
KeAi Communications Co., Ltd. |
| publishDate |
2022 |
| url |
https://doaj.org/article/6d004e3692a447fa8672c0d2cf7c8d45 |
| work_keys_str_mv |
AT chunhuili ionizablelipidassistedefficienthepaticdeliveryofgeneeditingelementsforoncotherapy AT tongrenyang ionizablelipidassistedefficienthepaticdeliveryofgeneeditingelementsforoncotherapy AT yuhuaweng ionizablelipidassistedefficienthepaticdeliveryofgeneeditingelementsforoncotherapy AT mengjiezhang ionizablelipidassistedefficienthepaticdeliveryofgeneeditingelementsforoncotherapy AT deyaozhao ionizablelipidassistedefficienthepaticdeliveryofgeneeditingelementsforoncotherapy AT shuaiguo ionizablelipidassistedefficienthepaticdeliveryofgeneeditingelementsforoncotherapy AT bohu ionizablelipidassistedefficienthepaticdeliveryofgeneeditingelementsforoncotherapy AT wanxuanshao ionizablelipidassistedefficienthepaticdeliveryofgeneeditingelementsforoncotherapy AT xiaoxiawang ionizablelipidassistedefficienthepaticdeliveryofgeneeditingelementsforoncotherapy AT abidhussain ionizablelipidassistedefficienthepaticdeliveryofgeneeditingelementsforoncotherapy AT xingjieliang ionizablelipidassistedefficienthepaticdeliveryofgeneeditingelementsforoncotherapy AT yuanyuhuang ionizablelipidassistedefficienthepaticdeliveryofgeneeditingelementsforoncotherapy |
| _version_ |
1718429902802255872 |