Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of<i>Angptl3</i>
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- Min Qiu
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155;
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- Zachary Glass
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155;
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- Jinjin Chen
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155;
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- Mary Haas
- Broad Institute of MIT and Harvard, Cambridge, MA 02142
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- Xin Jin
- Broad Institute of MIT and Harvard, Cambridge, MA 02142
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- Xuewei Zhao
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155;
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- Xuehui Rui
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155;
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- Zhongfeng Ye
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155;
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- Yamin Li
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155;
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- Feng Zhang
- Broad Institute of MIT and Harvard, Cambridge, MA 02142
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- Qiaobing Xu
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155;
説明
<jats:title>Significance</jats:title><jats:p>Genome editing technologies enable the permanent repair of disease-causing genetic mutations. However, the application of this technology has been limited by the technical challenge of achieving safe, effective, and specific in vivo delivery of the CRISPR-Cas9 genome editing components. Here, we report the development of a newly identified lipid nanoparticle (LNP) for specific delivery of CRISPR-Cas9 mRNA to the liver. While LNPs have been FDA approved for delivery of siRNA to the liver, here we examine their application for genome editing. When compared head-to-head, our delivery platform significantly outperforms the FDA-approved LNP in the efficient delivery of Cas9 mRNA for knockdown of the<jats:italic>Angptl3</jats:italic>gene and subsequent regulation of hypercholesterolemia, while matching the safety and specificity of the approved platform.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 118 (10), e2020401118-, 2021-03
Proceedings of the National Academy of Sciences
