{"id":{"repo_id":"mit","oai_identifier":"oai:dspace.mit.edu:1721.1/148610"},"canonical_url":"https://search.dev.ndltd.org/etd/mit/oai:dspace.mit.edu:1721.1/148610","repository":{"repo_id":"mit","name":"MIT","base_url":"https://dspace.mit.edu/oai/request"},"display":{"title":"Developing Nucleic Acid-Based Sensors and Actuators","abstract":"As the field of synthetic biology matures, engineers are tackling increasingly ambitious problems that require the integration of regulatory logic in complex environments. Nucleic acids are attractive molecules for designing sense-and-respond modules: they are ubiquitous, information-rich and interact with each other through simple rules. Here, through two examples, I show that nucleic acids are particularly suited to create programmable molecular tools, in which inputs and outputs are defined independently from each other. In the first half of this thesis, I describe the development of a strategy to design nucleic acid-responsive materials using the CRISPR-associated nuclease Cas12a as a user-programmable sensor and material actuator. I exploit the programmability of Cas12a to actuate hydrogels containing DNA as an anchor for pendant groups or as a structural element. This versatile approach improves on the sensitivity of current DNA-responsive materials while enabling their rapid repurposing toward new sequence targets. In the second half of this thesis, I describe how to engineer programmable single-transcript RNA sensors in vivo, in which adenosine deaminases acting on RNA (ADARs) autocatalytically convert target hybridization into a translational output. This system amplifies the signal from editing by endogenous ADAR through a positive feedback loop. This topology confers high dynamic range, low background, minimal off-target effects, and a small genetic footprint. I envision that the approaches described here have broad applications from basic science to advanced diagnostics and therapeutics, illustrating the great potential of programmable nucleic acid-based controllers.","abstract_html":"As the field of synthetic biology matures, engineers are tackling increasingly ambitious problems that require the integration of regulatory logic in complex environments. Nucleic acids are attractive molecules for designing sense-and-respond modules: they are ubiquitous, information-rich and interact with each other through simple rules. Here, through two examples, I show that nucleic acids are particularly suited to create programmable molecular tools, in which inputs and outputs are defined independently from each other. In the first half of this thesis, I describe the development of a strategy to design nucleic acid-responsive materials using the CRISPR-associated nuclease Cas12a as a user-programmable sensor and material actuator. I exploit the programmability of Cas12a to actuate hydrogels containing DNA as an anchor for pendant groups or as a structural element. This versatile approach improves on the sensitivity of current DNA-responsive materials while enabling their rapid repurposing toward new sequence targets. In the second half of this thesis, I describe how to engineer programmable single-transcript RNA sensors in vivo, in which adenosine deaminases acting on RNA (ADARs) autocatalytically convert target hybridization into a translational output. This system amplifies the signal from editing by endogenous ADAR through a positive feedback loop. This topology confers high dynamic range, low background, minimal off-target effects, and a small genetic footprint. I envision that the approaches described here have broad applications from basic science to advanced diagnostics and therapeutics, illustrating the great potential of programmable nucleic acid-based controllers.","abstract_has_math":false,"creators":["Gayet, Raphaël Vincent"],"institution":"Massachusetts Institute of Technology","degree_name":"Doctoral","degree_level":null,"degree_discipline":null,"degree_department":"Massachusetts Institute of Technology. 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Nucleic acids are attractive molecules for designing sense-and-respond modules: they are ubiquitous, information-rich and interact with each other through simple rules. Here, through two examples, I show that nucleic acids are particularly suited to create programmable molecular tools, in which inputs and outputs are defined independently from each other. In the first half of this thesis, I describe the development of a strategy to design nucleic acid-responsive materials using the CRISPR-associated nuclease Cas12a as a user-programmable sensor and material actuator. I exploit the programmability of Cas12a to actuate hydrogels containing DNA as an anchor for pendant groups or as a structural element. This versatile approach improves on the sensitivity of current DNA-responsive materials while enabling their rapid repurposing toward new sequence targets. In the second half of this thesis, I describe how to engineer programmable single-transcript RNA sensors in vivo, in which adenosine deaminases acting on RNA (ADARs) autocatalytically convert target hybridization into a translational output. This system amplifies the signal from editing by endogenous ADAR through a positive feedback loop. This topology confers high dynamic range, low background, minimal off-target effects, and a small genetic footprint. I envision that the approaches described here have broad applications from basic science to advanced diagnostics and therapeutics, illustrating the great potential of programmable nucleic acid-based controllers."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph.D."]},{"key":"dc:title","label":"Title","values":["Developing Nucleic Acid-Based Sensors and Actuators"]}]}],"canonical_facts":{"dc:contributor.advisor":["Collins, James J."],"dc:contributor.department":["Massachusetts Institute of Technology. Department of Biology","Massachusetts Institute of Technology. Microbiology Graduate Program"],"dc:creator":["Gayet, Raphaël Vincent"],"dc:date.accessioned":["2023-03-17T18:14:06Z"],"dc:date.available":["2023-03-17T18:14:06Z"],"dc:date.issued":["2022-09"],"dc:description.abstract":["As the field of synthetic biology matures, engineers are tackling increasingly ambitious problems that require the integration of regulatory logic in complex environments. Nucleic acids are attractive molecules for designing sense-and-respond modules: they are ubiquitous, information-rich and interact with each other through simple rules. Here, through two examples, I show that nucleic acids are particularly suited to create programmable molecular tools, in which inputs and outputs are defined independently from each other. In the first half of this thesis, I describe the development of a strategy to design nucleic acid-responsive materials using the CRISPR-associated nuclease Cas12a as a user-programmable sensor and material actuator. I exploit the programmability of Cas12a to actuate hydrogels containing DNA as an anchor for pendant groups or as a structural element. This versatile approach improves on the sensitivity of current DNA-responsive materials while enabling their rapid repurposing toward new sequence targets. In the second half of this thesis, I describe how to engineer programmable single-transcript RNA sensors in vivo, in which adenosine deaminases acting on RNA (ADARs) autocatalytically convert target hybridization into a translational output. This system amplifies the signal from editing by endogenous ADAR through a positive feedback loop. This topology confers high dynamic range, low background, minimal off-target effects, and a small genetic footprint. I envision that the approaches described here have broad applications from basic science to advanced diagnostics and therapeutics, illustrating the great potential of programmable nucleic acid-based controllers."],"dc:description.degree":["Ph.D."],"dc:identifier.uri":["https://hdl.handle.net/1721.1/148610"],"dc:publisher":["Massachusetts Institute of Technology"],"dc:rights":["In Copyright - Educational Use Permitted","Copyright MIT"],"dc:rights.uri":["http://rightsstatements.org/page/InC-EDU/1.0/"],"dc:title":["Developing Nucleic Acid-Based Sensors and Actuators"],"dc:type":["Thesis"],"thesis:degree_name":["Doctoral","Doctor of Philosophy"]},"updated_at":"2026-07-22T22:22:15Z"}