| The nascent field of mammalian synthetic biology holds the promise to revolutionize personalized medicine. The use of engineered genetic circuits for genome-wide screens, detecting and reporting molecular signatures, and targeting genetic mutations can redefine personalized medicine with specific applications ranging from discovery to therapy.;Genome-wide screens and experiments have been instrumental in unraveling cellular and disease properties. Here, we designed and validated a methodology for assembling transcription-activator like effector (TALE) libraries to target any DNA sequence of interest. Our method allows rapid library construction and genome-wide screens.;Combinations of molecular signals such as transcription factors and microRNAs (miRNAs) in cells are a reliable indicator of multi-gene disorders. A system capable of detecting these conditions in-situ may be used as a tool for diagnosis and monitoring of disease. Here, we engineered genetic sensors for combinations of endogenous transcription factors and miRNA. We interfaced our genetic sensors with colorimetric ELISA test strips. Our system allows low-cost, combinatorial, and in-situ reporting of molecular signatures.;Genome editing based on the clustered regularly interspaced short palindromic repeats (CRISPR) system has been expanding at a rapid pace and holds the promise of revolutionizing our ability to probe and edit the genome. We introduce a novel therapeutic technique to target a heterozygous gain-of-function mutation in KRAS. Disrupting the mutation caused the reversal of drug resistance to a MEK small-molecule inhibitor. This technology creates new opportunities for the treatment of a broad range of cancers and genetic diseases.;To summarize, we combine mammalian synthetic biology and genome editing to produce new technologies that advance the field of mammalian synthetic biology bringing us closer to personalized medicine applications in the areas of genetic screening, in-situ sensing, and finally therapeutic targeting. |
