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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.

 

We study equilibrium configurations of double-stranded DNA in a cylindrical viral capsid. The state of the encapsidated DNA consists of a disordered inner core enclosed by an ordered outer region, next to the capsid wall. The DNA configuration is described by a unit helical vector field, tangent to an associated centre curve, passing through properly selected locations. We postulate an expression for the energy of the encapsulated DNA based on that of columnar chromonic liquid crystals. A thorough analysis of the Euler–Lagrange equations yields multiple solutions. We demonstrate that there is a trivial, non-helical solution, together with two solutions with non-zero helicity of opposite sign. Using bifurcation analysis, we derive the conditions for local stability and determine when the preferred coiling state is helical. The bifurcation parameters are the ratio of the twist versus the bend moduli of DNA and the ratio between the sizes of the ordered and the disordered regions. 

Decades of motivation research have yielded a set of Motivation Design Principles (MDPs) that can be leveraged to support the development of student motivation and engagement in the classroom. This article addresses the translation of these guiding principles to teacher professional learning and subsequently, classroom practice. Drawing from published literature, as well as the experiences of a co-design team of motivation and science education researchers and middle school science teachers, we address the landscape of decision points for designing and implementing professional learning focused on supporting middle school students’ motivation in science. We identify 3 key decision points: (1) the extent to which professional learning should focus on general principles or specific practices; (2) the appropriate level(s) for translation of the MDPs into practice; and (3) the creation of opportunities for teacher reflection and self-assessment of their practice on student motivation and engagement.