Sonogenetic control of multiplexed genome regulation and base editing
Abstract Manipulating gene expression in the host genome with high precision is crucial for controlling cellular function and behavior. Here, we present a precise, non-invasive, and tunable strategy for controlling the expression of multiple endogenous genes both in vitro and in vivo, utilizing ultr...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42249-8 |
| _version_ | 1827709902015954944 |
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| author | Pei Liu Josquin Foiret Yinglin Situ Nisi Zhang Aris J. Kare Bo Wu Marina N. Raie Katherine W. Ferrara Lei S. Qi |
| author_facet | Pei Liu Josquin Foiret Yinglin Situ Nisi Zhang Aris J. Kare Bo Wu Marina N. Raie Katherine W. Ferrara Lei S. Qi |
| author_sort | Pei Liu |
| collection | DOAJ |
| description | Abstract Manipulating gene expression in the host genome with high precision is crucial for controlling cellular function and behavior. Here, we present a precise, non-invasive, and tunable strategy for controlling the expression of multiple endogenous genes both in vitro and in vivo, utilizing ultrasound as the stimulus. By engineering a hyper-efficient dCas12a and effector under a heat shock promoter, we demonstrate a system that can be inducibly activated through thermal energy produced by ultrasound absorption. This system allows versatile thermal induction of gene activation or base editing across cell types, including primary T cells, and enables multiplexed gene activation using a single guide RNA array. In mouse models, localized temperature elevation guided by high-intensity focused ultrasound effectively triggers reporter gene expression in implanted cells. Our work underscores the potential of ultrasound as a clinically viable approach to enhance cell and gene-based therapies via precision genome and epigenome engineering. |
| first_indexed | 2024-03-10T17:29:46Z |
| format | Article |
| id | doaj.art-7e18307bf8a7414cb4a83d6cc46380da |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:29:46Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-7e18307bf8a7414cb4a83d6cc46380da2023-11-20T10:04:19ZengNature PortfolioNature Communications2041-17232023-10-0114111110.1038/s41467-023-42249-8Sonogenetic control of multiplexed genome regulation and base editingPei Liu0Josquin Foiret1Yinglin Situ2Nisi Zhang3Aris J. Kare4Bo Wu5Marina N. Raie6Katherine W. Ferrara7Lei S. Qi8Molecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford UniversityMolecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford UniversityDepartment of Bioengineering, Stanford UniversityMolecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford UniversityMolecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford UniversityMolecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford UniversityMolecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford UniversityMolecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford UniversityDepartment of Bioengineering, Stanford UniversityAbstract Manipulating gene expression in the host genome with high precision is crucial for controlling cellular function and behavior. Here, we present a precise, non-invasive, and tunable strategy for controlling the expression of multiple endogenous genes both in vitro and in vivo, utilizing ultrasound as the stimulus. By engineering a hyper-efficient dCas12a and effector under a heat shock promoter, we demonstrate a system that can be inducibly activated through thermal energy produced by ultrasound absorption. This system allows versatile thermal induction of gene activation or base editing across cell types, including primary T cells, and enables multiplexed gene activation using a single guide RNA array. In mouse models, localized temperature elevation guided by high-intensity focused ultrasound effectively triggers reporter gene expression in implanted cells. Our work underscores the potential of ultrasound as a clinically viable approach to enhance cell and gene-based therapies via precision genome and epigenome engineering.https://doi.org/10.1038/s41467-023-42249-8 |
| spellingShingle | Pei Liu Josquin Foiret Yinglin Situ Nisi Zhang Aris J. Kare Bo Wu Marina N. Raie Katherine W. Ferrara Lei S. Qi Sonogenetic control of multiplexed genome regulation and base editing Nature Communications |
| title | Sonogenetic control of multiplexed genome regulation and base editing |
| title_full | Sonogenetic control of multiplexed genome regulation and base editing |
| title_fullStr | Sonogenetic control of multiplexed genome regulation and base editing |
| title_full_unstemmed | Sonogenetic control of multiplexed genome regulation and base editing |
| title_short | Sonogenetic control of multiplexed genome regulation and base editing |
| title_sort | sonogenetic control of multiplexed genome regulation and base editing |
| url | https://doi.org/10.1038/s41467-023-42249-8 |
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