Sonogenetic control of multiplexed genome regulation and base editing

Pei Liu, Josquin Foiret, Yinglin Situ, Nisi Zhang, Aris J. Kare, Bo Wu, Marina N. Raie, Katherine W. Ferrara () and Lei S. Qi ()
Additional contact information
Pei Liu: Stanford University
Josquin Foiret: Stanford University
Yinglin Situ: Stanford University
Nisi Zhang: Stanford University
Aris J. Kare: Stanford University
Bo Wu: Stanford University
Marina N. Raie: Stanford University
Katherine W. Ferrara: Stanford University
Lei S. Qi: Stanford University

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-42249-8

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