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dc.contributor.advisorWong, Wilsonen_US
dc.contributor.authorWeinberg, Benjaminen_US
dc.date.accessioned2018-11-14T18:21:57Z
dc.date.available2018-11-14T18:21:57Z
dc.date.issued2018
dc.identifier.urihttps://hdl.handle.net/2144/32592
dc.description.abstractEndowing cells with enhanced decision-making capacities is essential for creating smarter therapeutics and for dissecting phenotypes. Implementation of synthetic gene circuits affords a means for enhanced cellular control and genetic processing; however, genetic circuits for mammalian cells often require extensive fine-tuning to perform as intended. Here, a robust, general, and scalable system, called 'Boolean logic and arithmetic through DNA excision' (BLADE) is presented that is used to engineer genetic circuits with multiple inputs and outputs in mammalian cells with minimal optimization. The reliability of BLADE arises from its reliance on site-specific recombinases that regulate genes under the control of a single promoter that integrates circuit signals on a single transcriptional layer. Using BLADE, >100 circuits were tested in human embryonic kidney and Jurkat T cells and a quantitative metric was used to evaluate their performance. The circuits include a 3-input, two-output full adder; a 6-input, one-output Boolean logic look-up table; and circuits that incorporate CRISPR–Cas9 to regulate endogenous genes. Moreover, a large library of over 15 small-molecule, light and temperature-inducible recombinases has been established for fine-tuned control. BLADE enables execution of sophisticated cellular computation in mammalian cells, with applications in cell and tissue engineering.en_US
dc.language.isoen_US
dc.subjectBiomedical engineeringen_US
dc.titleEngineering biocomputers in mammalian cellsen_US
dc.typeThesis/Dissertationen_US
dc.date.updated2018-10-23T01:01:30Z
etd.degree.nameDoctor of Philosophyen_US
etd.degree.leveldoctoralen_US
etd.degree.disciplineBiomedical Engineeringen_US
etd.degree.grantorBoston Universityen_US


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