Abstract: The present disclosure generally relates to sugar reduction in foods and, in some aspects, to enzyme-polymer conjugated particles for food and other applications. Certain aspects of the disclosure are directed to compositions for reducing sugar content and/or producing dietary fiber within food products during or after consumption (e.g., in a subject's gastrointestinal (GI) tract), while maintaining the sweetness and flavor of the sugar in food products upon consumption (e.g., in a subject's mouth). For example, in one set of embodiments, a composition may comprise a particle comprising an enzyme capable of converting a sugar into a relatively non-digestible form (e.g., a polymer), optionally an inhibitor that reversibly inhibits the enzyme from converting the sugar, and optionally an additive capable of associating with the inhibitor. The composition may be used for in situ conversion of sugars upon exposure to an environment condition (e.g., pH and/or temperature) in the GI tract.

Abstract: Genetic circuits that control transgene expression in response to pre-defined transcriptional cues would enable the development of smart therapeutics. The present disclosure relates to engineered programmable single-transcript RNA sensors in which adenosine deaminases acting on RNA (ADARs) autocatalytically convert trigger hybridization into a translational output. This system amplifies the signal from editing by endogenous ADAR through a positive feedback loop. Amplification is mediated by the expression of a hyperactive, minimal ADAR variant and its recruitment to the edit site via an orthogonal RNA targeting mechanism. This topology confers high dynamic range, low background, minimal off-target effects, and a small genetic footprint. The circuits and systems disclosed herein leverage an ability to detect single nucleotide polymorphisms and modulate translation in response to endogenous transcript levels in mammalian cells.

Abstract: Provided herein are compositions and methods comprising engineered microorganisms and their use for locally degrading an antibiotic in the gastrointestinal tract to prevent or limit death of beneficial flora.

Abstract: The invention provides novel and versatile classes of riboregulators, including inter alia activating and repressing riboregulators, switches, and trigger and sink RNA, and methods of their use for detecting RNAs in a sample such as a well and in modulating protein synthesis and expression.

Abstract: Embodiments disclosed herein provide artificial expression systems comprising multivalent transcription factor complexes for cooperative transcription factor assembly and modulating gene expression. More specifically, engineered synthetic transcription factors are recruited and structurally organized on synthetic gene circuits using molecular clamps, where the strength of intra-complex interactions can be modulated for fine tuning of gene expression as desired.

Abstract: Embodiments disclosed herein provide artificial expression systems comprising multivalent transcription factor complexes for cooperative transcription factor assembly and modulating gene expression. More specifically, engineered synthetic transcription factors are recruited and structurally organized on synthetic gene circuits using molecular clamps, where the strength of intra-complex interactions can be modulated for fine tuning of gene expression as desired.

Abstract: Provided herein are compositions and methods to improve treatment of chronic infections, and reduce, delay, or inhibit formation of biofilms, using specific combinations of aminoglycoside antibiotics and treatment with one or more proton motive force (PMF) stimulating compounds. These novel methods are easily adapted to clinical settings as toxicity and efficacy of the antibiotics and metabolites used have already been studied in vivo, and as dosing for both the antibiotics and metabolites are known.

Abstract: The present disclosure provides genetic constructs comprising a recombinant internal ribosome entry site (IRES), which may be used as riboswitches to modulate translation of an operably-mRNA sequence encoding a protein of interest. In other aspects, the disclosure provides recombinant cells, methods, kits and systems that utilize the same, e.g., to provide a platform for modulating the expression of essentially any protein of interest in a eukaryotic cell.

Abstract: This disclosure provides riboregulators specific for particular viruses or for particular human transcription factors. The viral-specific riboregulators may be used to detect the presence of the particular virus, and this may enable diagnosis of an infection. The transcription factor specific riboregulators may be used to detect the presence and/or measure the level of the particular transcription factor, and this may enable diagnosis or prognosis of a particular condition such as cancer.

Abstract: Embodiments of various aspects described herein are directed to assays and devices for detecting a target molecule in a sample. In particular, there is described a lateral assay comprising a plurality of serially oriented capture zones, where each capture zone independently comprises an immobilized competitive molecule on a lateral flow matrix. The immobilized competitive molecule and the analyte competitively bind with a capture agent capable of binding the analyte.

Abstract: Methods for detecting the presence of a pathogen infection are described. In particular, this document provides a method of detecting target nucleic acids, such as pathogen-specific RNA, in a biological sample obtained from a subject, where the method comprises using one or more toehold switch sensors and an isothermal amplification step to detect the target nucleic acid. Methods specific for detecting and identify the presence of a virus such as Zika virus are also provided.

Abstract: This disclosure is generally directed to electrochemical readout of rapid diagnostics related to use of CRISPR effector systems. In one aspect, the disclosure provides a nucleic acid detection system. Generally, the system comprises: (1) a detection CRISPR system comprising an effector protein and one or more guide nucleic acid (gNA) strands designed to bind to corresponding target nucleic acid molecules; (2) an effector strand and (3) an electrode.

Abstract: Provided herein, in some embodiments, are engineered phagemids that comprise at least one synthetic genetic circuit, wherein the at least one synthetic genetic circuit comprises gene sequences encoding at least one non-lytic antimicrobial peptides (AMPs) and/or antibacterial toxin proteins, a stable origin of replication, and a bacteriophage-packaging signal, wherein the engineered phagemid does not comprise some or all gene sequences encoding bacteriophage proteins required for assembly of a bacteriophage particle.

Abstract: Provided herein are systems, methods and compositions for rendering cells or the expression of an effector protein sensitive to a predetermined condition. In one aspect, cells can be rendered dependent upon the presence of an environmental agent, e.g., an exogenous agent, without which the cell will default to expression of a death protein and be killed. In another aspect, cells can be rendered sensitive to the presence of a set of predetermined conditions such that cells will only grow when two or more necessary exogenous agents are supplied, and without either of which, the cells are killed. In this aspect, hybrid transcription factors provide a vast array of possible predetermined conditions.

Abstract: The present disclosure provides compositions (e.g., pyrimidines) and methods capable of potentiating the effects of antimicrobial agents and/or antiviral agents against bacterial infections and/or viral infections, respectively. Methods of sensitizing bacteria to antimicrobial agents and/or antiviral agents, as well as pharmaceutical compositions and therapeutic/prophylactic methods directed at microbial infections and/or viral infections are also provided.

Abstract: Described herein are nucleic acid detection systems, devices, and kits having a CRISPR component comprising an effector protein and a guide RNA, and/or a polynucleotide encoding a guide RNA, that binds or hybridizes to a corresponding target molecule. Also described herein are methods that utilize these nucleic acid systems, devices, and kits.

Abstract: Provided herein are compositions and methods to improve treatment of chronic infections, and reduce, delay, or inhibit formation of biofilms, using specific combinations of aminoglycoside antibiotics and treatment with one or more proton motive force (PMF) stimulating compounds. These novel methods are easily adapted to clinical settings as toxicity and efficacy of the antibiotics and metabolites used have already been studied in vivo, and as dosing for both the antibiotics and metabolites are known.

Abstract: Methods for detecting the presence of a pathogen infection are described. In particular, this document provides a method of detecting target nucleic acids, such as pathogen-specific RNA, in a biological sample obtained from a subject, where the method comprises using one or more toehold switch sensors and an isothermal amplification step to detect the target nucleic acid. Methods specific for detecting and identify the presence of a virus such as Zika virus are also provided.

Abstract: The disclosed subject matter relates to compositions, systems, kits, and methods that typically comprise and/or utilize a lyophilized composition comprising components for performing in vitro transcription prepared by lyophilizing an aqueous composition that includes: (i) the one or more components for performing in vitro transcription; and (ii) a non-reducing polysaccharide at a concentration of at least about 40 mM and/or a sugar alcohol at a concentration of at least about 40 mM. In some embodiments, the lyophilized composition is prepared by lyophilizing an aqueous composition that comprises no more than 5% (v/v) glycerol.

Abstract: The invention provides novel and versatile classes of riboregulators, including inter alia activating and repressing riboregulators, switches, and trigger and sink RNA, and methods of their use for detecting RNAs in a sample such as a well and in modulating protein synthesis and expression.