Abstract: The present invention relates to a method for generating primers and/or probes for use in analyzing a sample which may comprise a pathogen target sequence comprising providing a set of input genomic sequence to one or more target pathogens, generating a set of target sequences from the set of input genomic sequences, identifying one or more highly conserved target sequences, and generating one or more primers, one or more probes, or a primer pair and probe combination based on the one or more conserved target sequences.

Abstract: The present invention generally relates to systems and methods for imaging or determining nucleic acids, for instance, within cells. In some embodiments, the transcriptome of a cell may be determined. Certain embodiments are directed to determining nucleic acids, such as mRNA, within cells at relatively high resolutions. In some embodiments, a plurality of nucleic acid probes may be applied to a sample, and their binding within the sample determined, e.g., using fluorescence, to determine locations of the nucleic acid probes within the sample. In some embodiments, codewords may be based on the binding of the plurality of nucleic acid probes, and in some cases, the codewords may define an error-correcting code to reduce or prevent misidentification of the nucleic acids. In certain cases, a relatively large number of different targets may be identified using a relatively small number of labels, e.g., by using various combinatorial approaches.

Abstract: An optical component comprises a metasurface comprising nanoscale elements. The metasurface is configured to receive incident light and to generate optical outputs. The geometries and/or orientations of the nanoscale elements provide a first optical output upon receiving a polarized incident light with a first polarization, and provide a second optical output upon receiving a polarized incident light with a second polarization that is different from the first polarization.

Abstract: The present disclosure provides Cas9 variants, and base editors comprising these variants, that recognize non-canonical protospacer adjacent motifs (PAMs) and have less restrictive PAM requirements for editing. The present disclosure provides Cas9 protein variants comprising one or more amino acid substitutions relative to wild-type Nme2Cas9. Fusion proteins comprising the Cas protein variants described herein are also provided by the present disclosure. Further provided herein are methods for editing a target nucleic acid using the Cas variants and fusion proteins provided herein. The present disclosure also provides guide RNAs, complexes, polynucleotides, cells, kits, and pharmaceutical compositions. Further described herein are phage-assisted continuous evolution (PACE) systems, vectors, methods, and devices.

Abstract: Engineered bacteria that secrete therapeutic polypeptides, pharmaceutical compositions comprising the bacteria, methods for producing recombinant polypeptides, and methods for using the bacteria for diagnostic and therapeutic purposes are provided.

Abstract: Provided herein is a nucleic acid detection system comprising: a CRISPR system comprising an effector protein and one or more guide RNAs designed to bind to corresponding target molecules; an RNA-based masking construct; and optionally, nucleic acid amplification reagents to amplify target RNA molecules in a sample. In another aspect, the embodiments provide a polypeptide detection system comprising: a CRISPR system comprising an effector protein and one or more guide RNAs designed to bind a trigger RNA, an RNA-based masking construct; and one or more detection aptamers comprising a masked RNA polymerase promoter binding site or a masked primer binding site. In some embodiments, the system may be used to detect viruses in samples.

Abstract: In a general aspect, a photonic quantum network is disclosed. In some implementations, microwave modes and optical modes are generated on first and second quantum processing units (QPUs) by operation of a first transducer device of the first QPU and a second transducer device of the second QPU. The microwave modes are transmitted within the first and second QPUs from the first and second transducer devices to respective first and second qubit devices. The optical modes are transmitted from the first and second QPUs to an interferometer device. By operation of the interferometer device, output signals are generated on respective output channels based on the optical modes from the first and second QPUs. Based on the output signals detected by operation of photodetector devices coupled to the respective output channels, quantum entanglement transferred to the first and second qubit devices by the microwave modes is identified.

Abstract: The present invention features a method of reducing tactile dysfunction or anxiety in a subject diagnosed with Autism Spectrum Disorder, Rett Syndrome, or Fragile X syndrome by administering a GABAA agent having reduced blood brain barrier or by expressing a nucleic acid encoding an exogenous alpha or beta subunit of a GABAA receptor in dorsal root ganglion neurons in the subject using a vector.

Abstract: Provided herein, in some embodiments, are methods, compositions and kits for controlling nucleation and assembly of molecular nanostructures, microstructures and macrostructures.

Abstract: The present invention provides novel peripherally-restricted benzodiazepines with reduced blood brain barrier permeability and methods of use thereof for reducing tactile dysfunction, social impairment, and anxiety in a subject diagnosed with Autism Spectrum Disorder, Rett syndrome, Phelan McDermid syndrome, or Fragile X syndrome.

Abstract: Methods for quantifying DNA methylation that may be utilized for screening for diseases (e.g., cancer), diagnosing diseases (e.g., cancer type), monitoring progression of a disease, and monitoring response to a therapeutic treatment.

Abstract: Disclosed herein are methods, systems, and devices for oral drug delivery. The method generally involves orally administering a drug delivery device to the subject in need of treatment and triggering iontophoresis. The drug delivery device includes one or more active agents for delivery to the subject. The method can include the step of delivering the active agent to the intestinal mucosa after iontophoresis is triggered at the site, or simultaneously as iontophoresis is applied at the site. After the active agent(s) are delivered, the drug delivery device can be released from the intestinal mucosa. The iontophoresis can be performed for a period of time and at an electrical current that is effective to improve permeability of the one or more active agents across the intestine compared to orally administering the same drug delivery device in the absence of iontophoresis.

Abstract: Described herein are compositions comprising subsets of monocyte having distinct functional properties and methods for using the same to treat infectious disease.

Abstract: RNA editing tools for use in systems designed to measure RNA in vivo and manipulate specific cell types are disclosed herein. An RNA sensor system comprising a) a single-stranded RNA (ssRNA) sensor comprising a stop codon and a payload; optionally wherein the ssRNA sensor further comprises a normalizing gene; and b) an adenosine deaminase acting on RNA (ADAR) deaminase; wherein the sensor is capable of binding to a ssRNA target to form a double-stranded RNA (dsRNA) duplex that becomes a substrate for the ADAR deaminase; wherein the substrate comprises a mispairing within the stop codon; and wherein the mispairing is editable by the ADAR deaminase, which editing can effectively remove the stop codon so as to enable translation and expression of the payload. A method of quantifying ribonucleic acid (RNA) levels using the RNA sensor system is also disclosed.

Abstract: Provided herein are pluripotent stem cells comprising particular combinations of transcription factor for the production of oligodendrocyte progenitor cells (OPCs). Also provided herein are methods of producing the pluripotent stem cells and methods of using the pluripotent stem cells to produce (OPCs) and oligodendrocytes.

Abstract: The present invention generally relates to droplets and/or emulsions, such as multiple emulsions. In some cases, the droplets and/or emulsions may be used in assays, and in certain embodiments, the droplet or emulsion may be hardened to form a gel. In some aspects, a heterogeneous assay can be performed using a gel. For example, a droplet may be hardened to form a gel, where the droplet contains a cell, DNA, or other suitable species. The gel may be exposed to a reactant, and the reactant may interact with the gel and/or with the cell, DNA, etc., in some fashion. For example, the reactant may diffuse through the gel, or the hardened particle may liquefy to form a liquid state, allowing the reactant to interact with the cell. As a specific example, DNA contained within a gel particle may be subjected to PCR (polymerase chain reaction) amplification, e.g., by using PCR primers able to bind to the gel as it forms. As the DNA is amplified using PCR, some of the DNA will be bound to the gel via the PCR primer.

Abstract: The specification provides programmable base editors that are capable of introducing a nucleotide change and/or which could alter or modify the nucleotide sequence at a target site in mitochondrial DNA (mtDNA) with high specificity and efficiency. Moreover, the disclosure provides fusion proteins and compositions comprising a programmable DNA binding protein (e.g., a mitoTALE, a mitoZFP, or a CRISPR/Casp) and double-stranded DNA deaminase that is capable of being delivered to the mitochondria and carrying out precise installation of nucleotide changes in the mtDNA. The fusion proteins and compositions are not limited for use with mtDNA, but also may be used for base editing of any double-stranded target DNA.

Abstract: Aspects of the disclosure provide nucleic acids and compositions comprising gene regulatory elements (GREs) for specific expression in nociceptor cells. Other aspects of the disclosure relate to the use of vectors and compositions comprising the gene regulatory elements for treating or managing pain and other neurological diseases in a subject in need thereof.

Abstract: Described in embodiments herein are thiol-ene polymeric compositions that exhibit photo-induced, reversible switching between a solid (e.g., elastomeric) state and a liquid (e.g., flowable) state. The thiol-ene polymeric compositions may comprise a vinyl oligomer comprising at least two vinyl groups, a thiol oligomer comprising at least two thiol groups, and a Type I photoinitiator. In some embodiments, the composition comprises an excess of thiol groups relative to vinyl groups (e.g., a ratio of thiol groups to vinyl groups in the composition is at least 3:1). Reversible switching between the solid state and the liquid state may be induced through exposure of the composition to electromagnetic radiation (e.g., ultraviolet (UV) radiation). In some cases, reversible switching may be induced by a relatively low amount of energy (e.g., about 1 J/cm2 or less).

Abstract: Provided are methods of treating diabetes and/or obesity in a subject in need thereof, and methods of increasing the amount of cholic acid-7-sulfate (CA7S) in a subject. Further provided herein are methods of administering CA7S to a subject. Also provided are compositions and kits comprising cholic acid-7-sulfate, or a salt thereof for use in the treatment of diabetes and/or obesity.