Abstract:
The invention relates to methods and compositions that enable the rapid generation of high-order combinations of genetic elements, and that provide a barcoded basis for rapid characterization of the specific combination of genetic elements encoded within a single cell or in a pooled population.
Abstract:
The present invention is directed to engineered enzymatically active bacteriophages that are both capable of killing the bacteria by lysis and dispersing the bacterial biofilm because they have been also engineered to express biofilm-degrading enzymes, particularly dispersin B (DspB), an enzyme that hydrolyzes β-1,6-N-acetyl-D-glucosamine, a crucial adhesion molecule needed for biofilm formation and integrity in Staphylococcus and E. coli, including E. coli K-12, as well as clinical isolates.
Abstract:
Described are methods and compositions for the detection of target genes. The inventors have developed a synthetic nucleic acid sensor-effector gene circuit. In cells without a target gene, the circuit suppresses e.g., effector production, but in the presence of the target gene the suppression is subject to competition, such that the synthetic sensor is de-repressed and permits expression of the effector gene. The methods and compositions described further permit the selective expression of an effector gene in those cells expressing the target gene. In this manner, cells expressing a target gene can be selectively targeted for treatment or elimination. In certain aspects, the methods and compositions described permit the selective expression of an agent such as a therapeutic gene product, in a specifically targeted population of cells in an organism.
Abstract:
Disclosed herein are novel 5′ UTR sequences that can be used to control gene expression in various contexts. Also disclosed herein are methods of engineering 5′ UTR sequences and methods and kits for screening 5′ UTR sequences for a property of interest.
Abstract:
Provided herein, in some embodiments, are hydrogel-elastomer and hydrogel-alginate devices, compositions and associated methods to encapsulate living cells.
Abstract:
The disclosure provides compositions and methods for growing programmable enzyme-functionalized and sense-and-response bacterial cellulose living materials with engineered microbial co-cultures.
Abstract:
Transient molecules in the gastrointestinal (GI) tract, such as nitric oxide and hydrogen sulfide, are important signals and mediators of inflammatory bowel disease (IBD). Because these molecules may be short-lived in the body, they are difficult to detect. To track these reactive molecules in the GI tract, a miniaturized device has been developed that integrates genetically engineered probiotic biosensors with a custom-designed photodetector and readout chip. Leveraging the molecular specificity of living sensors, bacteria were genetically encoded to respond to IBD-associated molecules by luminescing. Low-power electronic readout circuits (e.g., using nanowatt power) integrated into the device convert the light from just 1 μL of bacterial culture into a wireless signal. Biosensor monitoring was demonstrated in the GI tract of small and large animal models and integration of all components into a sub-1.4 cm3 ingestible form factor capable of supporting wireless communication. The wireless detection of short-lived, disease-associated molecules may support earlier diagnosis of disease than is currently possible, more accurate tracking of disease progression, and more timely communication between patient and their care team supporting remote personalized care.
Abstract:
Described herein are methods and compositions that enable rapid generation of high-order combinations of genetic elements comprising a CRISPR guide sequence and a scaffold sequence, and a barcode for rapid identification of the combination of genetic elements encoded within a single cell or a pooled population. Also described herein compositions of inhibitors of epigenetic genes and methods for reducing cell proliferation and/or treating cancer.
Abstract:
Disclosed herein are novel synthetic bacteriophages and bacteriophage compositions, methods of production thereof, and therapeutic uses thereof.
Abstract:
Various aspects and embodiments of the present disclosure are directed to methods and compositions for functionalizing endogenous bacteria in vivo. The methods include delivering to endogenous bacterial cells a recombinant bacteriophage or phagemid that is engineered to contain at least one genetic circuit.