Abstract: The application provides devices, kits and methods for a streamlined lateral flow assay for sample preparation, optional amplification, and detection of a target nucleic acid using programmable nuclease reagents.

Abstract: Described herein are methods, devices, systems, and compositions for detecting a target nucleic acid using a programmable nuclease and a signal amplifier. Such methods, devices, systems, and compositions can comprise using signal amplifiers, such as catalytic oligonucleotides, which can be activated by programmable nucleases and be configured to cleave a reporter molecule upon activation. Signals can be generated and detected upon cleavage of reporter molecules.

Abstract: Provided herein, in certain embodiments, are various methods, reagents, and devices for detection of multiple target nucleic acids in a sample, or multiple segments of a target nucleic acid in a sample, using a programmable nuclease. In certain embodiments, the present disclosure provides compositions of pools of guide nucleic acids, programmable nucleases, and detector nucleic acids and methods of using said compositions for detection of different segments of one target nucleic acid or different target nucleic acids in a sample.

Abstract: Described herein, in certain embodiments, are methods of assaying for a segment of a coronavirus target nucleic acid in a sample. In some embodiments, the target nucleic acid is from a gene of SARS-CoV-2, or a variant thereof. In some embodiments, methods described herein comprise a) contacting the sample to: i) a detector nucleic acid; and ii) a composition comprising a programmable nuclease and a non-naturally occurring guide nucleic acid, and b) assaying for a change in a signal, wherein the change in the signal is produced by cleavage of the detector nucleic acid by the programmable nuclease. Also provided herein are devices for performing the methods of assaying for a segment of a coronavirus target nucleic acid described herein.

Abstract: The present disclosure provides compositions and methods of use for Type V CRISPR/Cas proteins. Type V CRISPR/Cas nucleases may be configured to bind nucleic acids in a sequence specific manner. Such a binding event may activate the Type V CRISPR/Cas nuclease for sequence non-specific trans-collateral cleavage of single-stranded nucleic acids. Provided herein are methods leveraging Type V CRISPR/Cas nuclease trans-collateral cleavage for identifying nucleic acid sequences.

Abstract: Described herein are devices, systems, fluidic devices, kits, and methods for detection of target nucleic acids associated with diseases, cancers, genetic disorders, a genotype, a phenotype, or ancestral origin. The devices, systems, fluidic devices, kits, and methods may comprise reagents of a guide nucleic acid targeting a target nucleic acid, a programmable nuclease, and a single stranded detector nucleic acid with a detection moiety. The target nucleic acid of interest may be indicative of a disease, and the disease may be communicable diseases, or of a cancer or genetic disorder. The target nucleic acid of interest may be indicative of a genotype, a phenotype, or ancestral origin.

Abstract: Disclosed herein are systems and methods for providing a high-throughput DETECTR assay in a single chamber. The single chamber may be one well of a microplate, and multiple assays may be conducted in a staggered fashion in separate chambers. The methods described herein implement a process including lysing a sample, isolating nucleic acid molecules, eluting the nucleic acid molecules, amplifying the nucleic acid molecules, and detecting a presence of a target nucleic acid.

Abstract: Described herein are devices, systems, fluidic devices, kits, and methods for detection of target nucleic acids associated with diseases, cancers, genetic disorders, a genotype, a phenotype, or ancestral origin. The devices, systems, fluidic devices, kits, and methods may comprise reagents of a guide nucleic acid targeting a target nucleic acid, a programmable nuclease, and a single stranded detector nucleic acid with a detection moiety. The target nucleic acid of interest may be indicative of a disease, and the disease may be communicable diseases, or of a cancer or genetic disorder. The target nucleic acid of interest may be indicative of a genotype, a phenotype, or ancestral origin.

Abstract: Described herein are methods and systems for direct detection of DNA nucleic acids using a DNA-activated programmable RNA nuclease.

Abstract: Described herein are devices, systems, fluidic devices, kits, and methods for detection of target nucleic acids.

Abstract: Described herein are methods to detect nucleic acid modifications, such as methylated DNA or methylated RNA, using a programmable nuclease. The present disclosure further provides compositions and methods for generating and amplifying ssDNA from target nucleic acid sequences, or templates, for activation of programmable nucleases. Further provided herein are methods of coupling ssDNA amplification and activation of programmable nucleases with programmable nuclease systems, such as DETECTR systems, including trans cleavage of detector nucleic acids to produce a signal indicating the presence of the target nucleic acid sequence.

Abstract: Disclosed herein are compositions, kits, and methods related to improved Cas activity. Through compositions and kits disclosed herein and practice of methods disclosed herein, one attains improved Cas activity such as Cas12 activity relative to Cas proteins in the art such as LbCas12. Further described herein are methods to detect target nucleic acid using a programmable nuclease system. Often, the target nucleic acids are present in at low frequency in the sample. Provided herein are methods for enriching these target nucleic acids for detection. Also described herein are methods to insert a PAM sequence into a target sequence of interest for use in a detection comprising a programmable nuclease.

Abstract: Described herein are devices, systems, fluidic devices, kits, and methods for detection of target nucleic acids associated with diseases, cancers, genetic disorders, a genotype, a phenotype, or ancestral origin. The devices, systems, fluidic devices, kits, and methods may comprise reagents of a guide nucleic acid targeting a target nucleic acid, a programmable nuclease, and a single stranded detector nucleic acid with a detection moiety. The target nucleic acid of interest may be indicative of a disease, and the disease may be communicable diseases, or of a cancer or genetic disorder. The target nucleic acid of interest may be indicative of a genotype, a phenotype, or ancestral origin.

Abstract: Described herein are devices, systems, fluidic devices, kits, and methods for detection of target nucleic acids associated with diseases, cancers, genetic disorders, a genotype, a phenotype, or ancestral origin. The devices, systems, fluidic devices, kits, and methods may comprise reagents of a guide nucleic acid targeting a target nucleic acid, a programmable nuclease, and a single stranded detector nucleic acid with a detection moiety. The target nucleic acid of interest may be indicative of a disease, and the disease may be communicable diseases, or of a cancer or genetic disorder. The target nucleic acid of interest may be indicative of a genotype, a phenotype, or ancestral origin.

Abstract: Described herein are devices, systems, fluidic devices, kits, and methods for detection of target nucleic acids associated with diseases, cancers, genetic disorders, a genotype, a phenotype, or ancestral origin. The devices, systems, fluidic devices, kits, and methods may comprise reagents of a guide nucleic acid targeting a target nucleic acid, a programmable nuclease, and a single stranded detector nucleic acid with a detection moiety. The target nucleic acid of interest may be indicative of a disease, and the disease may be communicable diseases, or of a cancer or genetic disorder. The target nucleic acid of interest may be indicative of a genotype, a phenotype, or ancestral origin.

Abstract: Disclosed herein are compositions, kits, and methods related to improved Cas activity. Through compositions and kits disclosed herein and practice of methods disclosed herein, one attains improved Cas activity such as Cas12 activity relative to Cas proteins in the art such as LbCas12. Further described herein are methods to detect target nucleic acid using a programmable nuclease system. Often, the target nucleic acids are present in at low frequency in the sample. Provided herein are methods for enriching these target nucleic acids for detection. Also described herein are methods to insert a PAM sequence into a target sequence of interest for use in a detection comprising a programmable nuclease.

Abstract: Described herein are devices, systems, fluidic devices, kits, and methods for detection of target nucleic acids associated with diseases, cancers, genetic disorders, a genotype, a phenotype, or ancestral origin. The devices, systems, fluidic devices, kits, and methods may comprise reagents of a guide nucleic acid targeting a target nucleic acid, a programmable nuclease, and a single stranded detector nucleic acid with a detection moiety. The target nucleic acid of interest may be indicative of a disease, and the disease may be communicable diseases, or of a cancer or genetic disorder. The target nucleic acid of interest may be indicative of a genotype, a phenotype, or ancestral origin.

Abstract: Described herein are devices, systems, fluidic devices, kits, and methods for detection of target nucleic acids associated with diseases, cancers, genetic disorders, a genotype, a phenotype, or ancestral origin. The devices, systems, fluidic devices, kits, and methods may comprise reagents of a guide nucleic acid targeting a target nucleic acid, a programmable nuclease, and a single stranded detector nucleic acid with a detection moiety. The target nucleic acid of interest may be indicative of a disease, and the disease may be communicable diseases, or of a cancer or genetic disorder. The target nucleic acid of interest may be indicative of a genotype, a phenotype, or ancestral origin.

Abstract: Disclosed herein are compositions, kits, and methods related to improved Cas activity. Through compositions and kits disclosed herein and practice of methods disclosed herein, one attains improved Cas activity such as Cas12 activity relative to Cas proteins in the art such as LbCas12. Further described herein are methods to detect target nucleic acid using a programmable nuclease system. Often, the target nucleic acids are present in at low frequency in the sample. Provided herein are methods for enriching these target nucleic acids for detection. Also described herein are methods to insert a PAM sequence into a target sequence of interest for use in a detection comprising a programmable nuclease.

Abstract: A method of manufacturing a cable harness may comprise the steps of providing a plurality of cables, wherein each cable comprises a cable inner and a coating, wherein each cable inner comprises at least one conductor, locating at least a portion of each of the plurality of cables within a mould tool, heating the portions of each of the plurality of cables such that the coating of each cable consolidates to form a common harness with a solid cross section, wherein the cable inners are arranged within the common harness.