Acoustically triggered mechanotherapy using genetically encoded gas vesicles

Bar‐Zion, Avinoam; Nourmahnad, Atousa; Mittelstein, David R.; Shivaei, Shirin; Yoo, Seung Jick; Buss, Marjorie T.; Hurt, Robert C.; Malounda, Dina; Abedi, Mohamad; Lee‐Gosselin, Audrey; Swift, Margaret; Maresca, David; Shapiro, Mikhail G.

doi:10.1038/s41565-021-00971-8

Cited by 102 publications

(82 citation statements)

References 66 publications

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“…[96,97] Thus, nanocage systems that do not require in vitro assembly, could be locally assembled in vivo and released. [96,98] Finally, Dps_Encs could themselves be imbued with cell targeting capabilities through the genetic fusion of cell penetrating peptides or similar targeting systems, to the encapsulin C-terminus exposed on the shell exterior. [33,52]…”

Section: Discussionmentioning

confidence: 99%

Engineered protein nanocages for concurrent RNA and protein packagingin vivo

Kwon

Giessen

2022

Preprint

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Protein nanocages have emerged as an important engineering platform for biotechnological and biomedical applications. Among naturally occurring protein cages, encapsulin nanocompartments have recently gained prominence due to their favorable physico-chemical properties, ease of shell modification, and highly efficient and selective intrinsic protein packaging capabilities. Here, we expand encapsulin function by designing and characterizing encapsulins for concurrent RNA and protein encapsulation in vivo. Our strategy is based on modifying encapsulin shells with nucleic acid binding peptides without disrupting the native protein packaging mechanism. We show that our engineered encapsulins reliably self-assemble in vivo, are capable of efficient size-selective in vivo RNA packaging, can simultaneously load multiple functional RNAs, and can be used for concurrent in vivo packaging of RNA and protein. Our engineered encapsulation platform has potential for co-delivery of therapeutic RNAs and proteins to elicit synergistic effects, and as a modular tool for other biotechnological applications.

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Section: Discussionmentioning

confidence: 99%

Engineered protein nanocages for concurrent RNA and protein packagingin vivo

Kwon

Giessen

2022

Preprint

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“…[63][64][65][66] In addition, the spatial distribution is important in guiding focused energy procedures applied to the cells, such as focused ultrasound. [67][68][69] Other potential applications include the study of the gastrointestinal (GI) microbiome and the tracking of probiotics designed to diagnose or treat GI conditions. 70,71 In these applications, luminescence imaging would provide limited in vivo resolution due to light scattering, and would be difficult to scale to larger animals or human patients.…”

Section: Discussionmentioning

confidence: 99%

Genomically mined acoustic reporter genes enable real-timein vivomonitoring of tumors and tumor-homing probiotics

Hurt

Buss

Duan

et al. 2021

Preprint

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A major outstanding challenge in the fields of biological research, synthetic biology and cell-based medicine is the difficulty of visualizing the function of natural and engineered cells noninvasively inside opaque organisms. Ultrasound imaging has the potential to address this challenge as a widely available technique with a tissue penetration of several centimeters and a spatial resolution below 100 um. Recently, the first genetically encoded reporter molecules were developed based on bacterial gas vesicles to link ultrasound signals to molecular and cellular function. However, the properties of these first-generation acoustic reporter genes (ARGs) resulted in limited sensitivity and specificity for imaging in the in vivo context. Here, we describe second-generation ARGs with greatly improved acoustic properties and expression characteristics. We identified these ARGs through a systematic phylogenetic screen of candidate gas vesicle gene clusters from diverse bacteria and archaea. The resulting constructs offer major qualitative and quantitative improvements, including the ability to produce nonlinear ultrasound contrast to distinguish their signals from those of background tissues, and a reduced burden of expression in probiotic hosts. We demonstrate the utility of these next-generation ARGs by imaging the in situ gene expression of tumor-homing probiotic bacteria, revealing the unique spatial distribution of tumor colonization by these cells noninvasively in living subjects. *equal contribution

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“…In nature, tiny cavitation bubbles can be used as a weapon by a snapper shrimp to stun or even kill prey animals ( 5 , 6 ), whereas large bubbles produced by humpback whales form into a network for trapping prey animals. In practical applications, bubbles can be used as a passive protective layer to reduce hydrodynamic drag ( 7 , 8 ), as active energy carriers to dissipate heat ( 9 ) from hot surfaces through liquid-to-bubble phase transition, and kill cancer cells ( 10 ) through acoustic trigger. Despite these diverse applications, relatively less attention has been paid to collecting the kinetic energy abounded in these numerous moving bubbles.…”

Section: Introductionmentioning

confidence: 99%

Bubble energy generator

Yan

Deng

et al. 2022

Sci. Adv.

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Bubbles have been extensively explored as energy carriers ranging from boiling heat transfer and targeted cancer diagnosis. Yet, despite notable progress, the kinetic energy inherent in small bubbles remains difficult to harvest. Here, we develop a transistor-inspired bubble energy generator for directly and efficiently harvesting energy from small bubbles. The key points lie in designing dielectric surface with high-density electric charges and tailored surface wettability as well as transistor-inspired electrode configuration. The synergy between these features facilitates fast bubble spreading and subsequent departure, transforms the initial liquid/solid interface into gas/solid interface under the gating of bubble, and yields an output at least one order of magnitude higher than existing studies. We also show that the output can be further enhanced through rapid bubble collapse at the air/liquid interface and multiple bubbles synchronization. We envision that our design will pave the way for small bubble-based energy harvesting in liquid media.

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Acoustically triggered mechanotherapy using genetically encoded gas vesicles

Cited by 102 publications

References 66 publications

Engineered protein nanocages for concurrent RNA and protein packagingin vivo

Engineered protein nanocages for concurrent RNA and protein packagingin vivo

Genomically mined acoustic reporter genes enable real-timein vivomonitoring of tumors and tumor-homing probiotics

Bubble energy generator

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