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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
KeAi Publishing
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604671/ https://www.ncbi.nlm.nih.gov/pubmed/34853819 http://dx.doi.org/10.1016/j.bioactmat.2021.05.051 |
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author | Li, Chunhui Yang, Tongren Weng, Yuhua Zhang, Mengjie Zhao, Deyao Guo, Shuai Hu, Bo Shao, Wanxuan Wang, Xiaoxia Hussain, Abid Liang, Xing-Jie Huang, Yuanyu |
author_facet | Li, Chunhui Yang, Tongren Weng, Yuhua Zhang, Mengjie Zhao, Deyao Guo, Shuai Hu, Bo Shao, Wanxuan Wang, Xiaoxia Hussain, Abid Liang, Xing-Jie Huang, Yuanyu |
author_sort | Li, Chunhui |
collection | PubMed |
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 | Online Article Text |
id | pubmed-8604671 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | KeAi Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-86046712021-11-30 Ionizable lipid-assisted efficient hepatic delivery of gene editing elements for oncotherapy Li, Chunhui Yang, Tongren Weng, Yuhua Zhang, Mengjie Zhao, Deyao Guo, Shuai Hu, Bo Shao, Wanxuan Wang, Xiaoxia Hussain, Abid Liang, Xing-Jie Huang, Yuanyu Bioact Mater Article 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. KeAi Publishing 2021-06-25 /pmc/articles/PMC8604671/ /pubmed/34853819 http://dx.doi.org/10.1016/j.bioactmat.2021.05.051 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Li, Chunhui Yang, Tongren Weng, Yuhua Zhang, Mengjie Zhao, Deyao Guo, Shuai Hu, Bo Shao, Wanxuan Wang, Xiaoxia Hussain, Abid Liang, Xing-Jie Huang, Yuanyu Ionizable lipid-assisted efficient hepatic delivery of gene editing elements for oncotherapy |
title | 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_short | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604671/ https://www.ncbi.nlm.nih.gov/pubmed/34853819 http://dx.doi.org/10.1016/j.bioactmat.2021.05.051 |
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