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Acoustically Detonated Biomolecules for Genetically Encodable Inertial Cavitation

Bar-Zion, Avinoam and Nourmahnad, Atousa and Mittelstein, David R. and Yoo, Sangjin and Malounda, Dina and Abedi, Mohamad and Lee-Gosselin, Audrey and Maresca, David and Shapiro, Mikhail G. (2019) Acoustically Detonated Biomolecules for Genetically Encodable Inertial Cavitation. . (Unpublished)

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Recent advances in molecular engineering and synthetic biology have made it possible for biomolecular and cell-based therapies to provide highly specific disease treatment. However, both the ability to spatially target the action of such therapies, and their range of effects on the target tissue remain limited. Here we show that biomolecules and cells can be engineered to deliver potent mechanical effects at specific locations inside the body under the direction of focused ultrasound. This capability is based on gas vesicles, a unique class of air-filled protein nanostructures derived from buoyant photosynthetic microbes. We show that low-frequency ultrasound can convert these nanoscale biomolecules into micron-scale cavitating bubbles, as demonstrated with acoustic measurements and ultrafast optical microscopy. This allows gas vesicles targeted to cell-surface receptors to serve as remotely detonated cell-killing agents. In addition, it allows cells genetically engineered to express gas vesicles to be triggered with ultrasound to lyse and release therapeutic payloads. We demonstrate these capabilities in vitro, in cellulo, and in vivo. This technology equips biomolecular and cellular therapeutics with unique capabilities for spatiotemporal control and mechanical action.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper Paper
Bar-Zion, Avinoam0000-0002-7564-9467
Nourmahnad, Atousa0000-0001-5208-0020
Mittelstein, David R.0000-0001-8747-0483
Yoo, Sangjin0000-0002-0449-4242
Malounda, Dina0000-0001-7086-9877
Abedi, Mohamad0000-0001-9717-6288
Lee-Gosselin, Audrey0000-0002-2431-2741
Maresca, David0000-0002-4921-6406
Shapiro, Mikhail G.0000-0002-0291-4215
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. bioRxiv preprint first posted online Apr. 29, 2019. The authors thank Dan Piraner, Anupama Lakshmanan, Arash Farhadi, and Pradeep Ramesh for helpful discussions. We thank Arash Farhadi for help with the GvpC-RGD variant and Hunter Davis for input on HFR imaging optics. We thank Maayan Harel ( for the illustrations in this paper. We thank Alasdair McDowall for help with electron microscopy. This project was supported by the David and Lucile Packard Fellowship for Science and Engineering (MGS) and the Heritage Medical Research Institute (MGS). AB-Z is supported by the Marie Skłodowska-Curie Fellowship and the Lester Deutsch Fellowship. AN was supported by the Amgen Scholars program. MA is supported by the NSF Graduate Research Fellowship and the P.D. Soros Fellowship. D Maresca is supported by the Human Frontiers Science Program Cross-Disciplinary Fellowship. Author Contributions: AB-Z and MGS conceived the study. AB-Z, AN, D Maresca, DRM, and SY designed, planned and conducted in vitro experiments. AB-Z, AN, and AL-G designed, planned and conducted in vivo experiments. AB-Z edited the gene circuits with MA guidance. AB-Z, AN, DRM, SY, and D Maresca analyzed the data. D Malounda prepared the purified GVs. All authors discussed the results. AB-Z, AN, and MGS wrote the manuscript with input from all the authors. All the authors have given their approval for the final version of the manuscript. MGS supervised the research. The authors declare no competing financial interests.
Group:Heritage Medical Research Institute
Funding AgencyGrant Number
David and Lucile Packard FoundationUNSPECIFIED
Heritage Medical Research InstituteUNSPECIFIED
Marie Curie FellowshipUNSPECIFIED
Lester Deutsch FellowshipUNSPECIFIED
NSF Graduate Research FellowshipUNSPECIFIED
Paul and Daisy Soros FellowshipUNSPECIFIED
Human Frontier Science ProgramUNSPECIFIED
Record Number:CaltechAUTHORS:20190429-085425670
Persistent URL:
Official Citation:Acoustically Detonated Biomolecules for Genetically Encodable Inertial Cavitation. Avinoam Bar-Zion, Atousa Nourmahnad, David Mittelstein, Sangjin Yoo, Dina Malounda, Mohamad Abedi, Audrey Lee-Gosselin, David Maresca, Mikhail G. Shapiro. bioRxiv 620567; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:95067
Deposited By: Tony Diaz
Deposited On:29 Apr 2019 17:24
Last Modified:22 Nov 2019 20:55

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