Abstract: The present disclosure relates to compositions of matter and assay methods used to detect one or more target nucleic acids of interest in a sample. The compositions and methods provide signal boost upon detection of target nucleic acids of interest in less than one minute and in some instances instantaneously at ambient temperatures down to 16° C. or less, without amplification of the target nucleic acids yet allowing for massive multiplexing, high accuracy and minimal non-specific signal generation.

Abstract: The present invention comprises Rig I agonists for enhancing the effects of cytotoxic cells and stem Cells. The Rig I agonists can be used in vivo as small molecule therapeutics or in vitro to enhance cells for adoptive cell transfer. Applications include cancer therapy, immune system enhancement, chronic viral infection and treatment of viral induced inflammation and enhancement of virus based therapies.

Abstract: Presented herein are methods and compositions for concatenating template strands during the bridge amplification process. The methods are useful for surface amplification at improved densities. The methods and compositions provided herein enable creation of clusters that are brighter, but at the same densities as currently achieved using standard cluster amplification.

Abstract: The invention provides methods and apparatus for carrying out multiple amplification reactions in a single reaction chamber by successive cycles of loading reaction mixture, amplifying, and removing spent reaction mixture in a fluidly closed reaction system. In particular, the present invention allows amplification of a plurality of target polynucleotides from a single sample by carrying out under closed-loop control successive amplifications of different target polynucleotides from different portions of the sample.

Abstract: The present invention is a method for measuring the amount of at least one molecule in a biological sample, the method comprising a) combining the sample, or a derivative thereof, with one or more aptamers and allowing one or more molecules in the sample to bind to the aptamer(s); b) separating bound from unbound molecules; and c) quantifying the molecule(s) bound to the or each aptamer, wherein quantification of the bound molecule(s) is carried out by sequencing at least part of the or each aptamer. Uses of and products derived from the method are also contemplated.

Abstract: This application provides a kit or a device for detection of ovarian tumor, comprising a nucleic acid(s) for detecting a miRNA(s) in a sample from a subject, and a method for detecting ovarian tumor, comprising measuring the miRNA(s) in vitro.

Abstract: The invention includes methods and compositions for the treatment and prevention of a disease or condition resulting from dysregulation of USB1 and resulting expression of downstream miRNAs. In one preferred embodiment, the invention may include inhibiting the expression or activity of USB1 resulting in the downregulation of downstream miRNA expression. In alternative embodiments, the invention includes methods and compositions for the treatment and prevention of a disease or condition resulting from dysregulation of miRNAs downstream of USB1, namely through the inhibition of PAPD5 and/or PAPD7, resulting in the upregulation of said downstream miRNA expression.

Abstract: A method, software, database, and system in which a query attribute is used as the basis for accessing stored attribute combinations and their frequencies of occurrence for individuals; and tabulating, based on frequencies of occurrence, those attribute combinations that are most likely to co-occur with the query attribute.

Abstract: Disclosed is a method for treating endometriosis, preventing endometriosis, or ameliorating a symptom of endometriosis in a subject comprising the step of administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising as an active ingredient a therapeutic dsRNA (tdsRNA).

Abstract: Provided herein are materials and methods for efficiently delivering nucleic acids to cochlear and vestibular cells.

Abstract: The invention provides seed and plants of corn hybrid SVSA5142 and the parent lines thereof. The invention thus relates to the plants, seeds, and tissue cultures of corn hybrid SVSA5142 and the parent lines thereof and to methods for producing a corn plant produced by crossing such plants with themselves or with another corn plant, such as a plant of another genotype. The invention further relates to seeds and plants produced by such crossing. The invention further relates to parts of such plants, including the fruit and gametes of such plants.

Abstract: The present disclosure relates to methods of treating heat shock factor 1 (HSF1)-related diseases such as cancer and viral diseases, using a therapeutically effective amount of a RNAi agent to HSF.

Abstract: Described herein are variants of alpha-hemolysin having at least one amino acid substitution at H35G, E111N, M113A, and/or K147N in the mature, wild-type alpha-hemolysin amino acid sequence. In certain examples, the variant may have a substitution at E111S, M113S, T145S, K147S, or L135I in the mature alpha-hemolysin amino acid sequence. The ?-hemolysin variants may also include a substitution at H144A and/or a series of glycine residues spanning residues 127 to 131 of the mature, wild-type alpha hemolysin. Also provided are nanopore assemblies including the alpha-hemolysin variants, the assembly having an increased nanopore lifetime. Further, provided are variants that, in addition to providing increased lifetime, provide a decreased time-to-thread. Hence, the variants provided herein both increase nanopore lifetime and improve efficiency and accuracy of DNA sequencing reactions using nanopores comprising the variants.

Abstract: The present disclosure relates to methods of detecting and treating inherited neuropathy.

Abstract: The present invention relates to methods for shifting the splicing profile of the DUX4 gene, a double homeobox gene on human chromosome 4q35. Recombinant adeno-associated viruses of the invention deliver DNAs encoding U7-based small nuclear RNAs to induce DUX4 exon-skipping and the expression of shortened forms of DUX4. The methods have application in the treatment of muscular dystrophies such as facioscapulohumeral muscular dystrophy.

Abstract: The present disclosure discloses a detection kit for Salmonella typhi, a preparation method and an application thereof, the detection kit includes: amplification primer, crRNA, LbCas12a-RR protein and a single-stranded DNA reporting system, the crRNA is a specific crRNA for a detection segment of the flag gene of Salmonella typhi; a LbCas12a-RR protein expression sequence is a prokaryotic codon optimized with a Cas12 protein nucleic acid sequence, and amino acid positions of 532 and 595 are mutated into G532R and K595R, respectively. The application of the kit is, to use the detection kit of Salmonella typhi for nucleic acid detection of Salmonella typhi; and the kit has high sensitivity, high specificity and fast visualization.

Abstract: The present invention relates to novel protein pores and their uses in analyte detection and characterisation. The invention particularly relates to an isolated pore complex formed by a CsgG-like pore and a modified CsgF peptide, or a homologue or mutant thereof, thereby incorporating an additional channel constriction or reader head in the nanopore. The invention further relates to a transmembrane pore complex and methods for production of the pore complex and for use in molecular sensing and nucleic acid sequencing applications.

Abstract: Lipid nanoparticle (LNP) encapsulating self-amplifying mRNA, compositions, and methods of using the novel nucleic acid constructs and compositions are disclosed. LNP constructs include novel ionizable lipid. Novel sa-mRNA constructs encode a modified SARS-CoV-2 spike protein, wherein the polynucleotide has been truncated to not include nucleotides encoding a SARS-CoV-2 transmembrane domain and short cytosolic domain amino acids and immunomodulators. Sa-mRNAs are useful in for use as a therapeutic, diagnostic and/or prophylactic agent to mammalian cells or organs.

Abstract: The present invention relates to hybrid nucleic acid sequence constructs comprising a CRISPR nucleic acid sequence and a DNA repair template associated with each other in a covalent and/or non-covalent way for CRISPR based genome engineering. Further provided is a molecular complex additionally comprising at least one CRISPR polypeptide. All components within the complex are in physical proximity. In addition, there is provided a plant, plant cell, a plant material, or a derivative, or progeny thereof comprising the hybrid RNA/DNA sequence and/or the molecular complex. Further, there is provided a method for modifying at least one DNA target sequence in a prokaryotic or eukaryotic cell as well as a method for manufacturing a plant or plant cell. Finally, there is provided the use of at least one hybrid RNA/DNA sequence, or use of a molecular complex for gene editing or genome engineering in a prokaryotic or eukaryotic cell or organism.

Abstract: Systems and methods are provided for trapping and electrically monitoring molecules in a nanopore sensor. The nanopore sensor comprises a support structure with a first and a second fluidic chamber, at least one nanopore fluidically connected to the two chambers, and a protein shuttle. The protein shuttle comprises an electrically charged protein molecule, such as Avidin. The nanopore can be a Clytosolin A. A method can comprise applying a voltage across the nanopores to draw protein shuttles towards the nanopores. The ionic current through each or all of the nanopores can be concurrently measured. Based on the measured ionic current, blockage events can be detected. Each blockage event indicates a capture of a protein shuttle by at least one nanopore. Each blockage event can be detected through a change of the total ionic current flow or a change in the ionic current flow for a particular nanopore.

Abstract: A method for sequencing a nucleic acid template includes: (a) performing a first sequencing process including flowing nucleotides and/or reagents to the nucleic acid template according to a first predetermined ordering of nucleotides and/or reagents to obtain a first sequencing result; (b) after the first sequencing process, performing a second sequencing process including flowing nucleotides and/or reagents to the nucleic acid template according to a second predetermined ordering of nucleotides and/or reagents to obtain a second sequencing result, the second predetermined ordering of nucleotides and/or reagents being different from the first predetermined ordering of nucleotides and/or reagents and at least one of the first and second predetermined orderings of nucleotides and/or reagents being designed for repeat sequencing; and (c) determining a sequence of bases corresponding to at least a portion of the nucleic acid template using both the first sequencing result and the second sequencing result.

Abstract: A method for amplifying a target nucleic acid including providing a system having a crRNA or a derivative thereof, and a Cas protein or a variant thereof. The crRNA or the derivative thereof contains a target-specific nucleotide region substantially complementary to a region of the target nucleic acid, and contacting the target nucleic acid with the system to form a complex.

Abstract: A computer-implemented method for spectroscopic analysis of biological material is provided that includes analyzing samples of biological material from a plurality of sources, and delivering samples of biological material to at least one flow cell for spectroscopy, and determining whether the spectroscopic analysis for each sample of the plurality of samples is or is predicted to be ambiguous in that it is affected by at least two non-discriminable factors. If such a determination is made, a disambiguating step can be performed.

Abstract: The invention relates to a specific panel of circulating synaptic protein related miRNAs for use in the diagnosis of Mild Cognitive Impairment (MCI) and/or early diagnosis of Alzheimer's disease (AD). The invention also relates to a method and to a kit for the diagnosis of said diseases using said specific panel of circulating miRNAs biomarkers.

Abstract: Among the various aspects of the present disclosure is the provision of compositions and methods for selectively reducing pathogenic isoforms (e.g., DNAJB6) in a subject having a neuromuscular disorder. An aspect of the present disclosure provides for selectively reducing DNAJB6 in a subject having a neuromuscular disorder (e.g., limb-girdle muscular dystrophy D1 (LGMD-D1)) comprising administering an amount of a DNAJB6-targeting antisense oligonucleotide (ASO) sufficient to reduce the expression of DNAJB6 compared to the subject prior to being administered the DNAJB6-targeting ASO.

Abstract: The disclosure provides for methods to form compact cross-linked polynucleotide/protein structures that can then be labeled using a barcoded oligonucleotide array in order to reconstruct physical linkage and/or genomic proximity (and phase) of polynucleotide fragments.

Abstract: The invention relates to new methods for synthesising polynucleotide molecules according to a predefined nucleotide sequence. The invention also relates to methods for the assembly of synthetic polynucleotides following synthesis, as well as systems and kits for performing the synthesis and/or assembly methods.

Abstract: The invention generally relates to droplet based digital PCR and methods for analyzing a target nucleic acid using the same. In certain embodiments, methods of the invention involve forming sample droplets containing, on average, a single target nucleic acid, amplifying the target in the droplets, excluding droplets containing amplicon from the target and amplicon from a variant of the target, and analyzing target amplicons.

Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a G-alpha q subunit (GNAQ) of a heterotrimeric G gene, and methods of using the dsRNA to inhibit expression of GNAQ.

Abstract: The present disclosure relates to devices and methods for the detection and/or sorting of nucleic acids. Further disclosed are methods for device fabrication.

Abstract: The present disclosure provides methods of treating subjects having a liver disease, and methods of identifying subjects having an increased risk of developing liver disease.

Abstract: The present invention features a method and kit for isolating microvesicles or extracting microvesicle nucleic acids from a biological sample by using a control particle. The present invention provides control particles that are viruses or virus-like particles, such as bacteriophages, that contain control nucleic acids that can be detected to assess the accuracy, reliability, and efficiency of the microvesicle isolation or nucleic acid extraction steps. The methods described herein may further comprise the analysis of the presence, absence, or level of at least one biomarker associated with a disease or medical condition for diagnosing, prognosing, or monitoring the disease or medical condition.

Abstract: Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. The determination of the relative amounts may count sequences of only certain length. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists. Prior to sequencing, the biological sample may be enriched for DNA fragments of a particular sizes.

Abstract: Described herein are methods useful for incorporating one or more adaptors and/or nucleotide tag(s) and/or barcode nucleotide sequence(s) one, or typically more, target nucleotide sequences. In particular embodiments, nucleic acid fragments having adaptors, e.g., suitable for use in high-throughput DNA sequencing are generated. In other embodiments, information about a reaction mixture is encoded into a reaction product. Also described herein are methods and kits useful for amplifying one or more target nucleic acids in preparation for applications such as bidirectional nucleic acid sequencing. In particular embodiments, methods of the invention entail additionally carrying out bidirectional DNA sequencing. Also described herein are methods for encoding and detecting and/or quantifying alleles by primer extension.

Abstract: Methods for purifying RNA from a sample, comprising one or more steps of tangential flow filtration, hydroxyapatite chromatography, core bead flow-through chromatography, or any combinations thereof. These techniques are useful individually, but show very high efficiency when used in combination, or when performed in particular orders. The methods can purify RNA in a highly efficient manner without unduly compromising potency or stability, to provide compositions in which RNA is substantially cleared of contaminants. Moreover, they can be performed without the need for organic solvents.

Abstract: The present disclosure provides a system comprising a communication interface and computer for assigning a label to the biomolecule fingerprint, wherein the label corresponds to a biological state. The present disclosure also provides a sensor arrays for detecting biomolecules and methods of use. In some embodiments, the sensor arrays are capable of determining a disease state in a subject.

Abstract: Provided are methods of producing size-selected nucleic acid libraries. The methods include contacting a nucleic acid sample and a nucleic acid binding reagent including an affinity tag, under conditions in which nucleic acids of less than a desired length are substantially bound to the nucleic acid binding reagent and nucleic acids of the desired length are substantially not bound to the nucleic acid binding reagent. The conditions include the duration of the contacting, the concentration of the nucleic acid binding reagent, or both. The methods further include separating, using the affinity tag, the nucleic acids of less than the desired length bound to the nucleic acid binding reagent from the nucleic acids of the desired length not bound to the nucleic acid binding reagent, to produce a size-selected nucleic acid library. Compositions and kits that find use, e.g., in practicing the methods of the present disclosure, are also provided.

Abstract: Disclosed herein, inter alia, are compounds, compositions, and methods of use thereof in the sequencing of a nucleic acid.

Abstract: Disclosed herein include methods and compositions for nucleic acid synthesis using a terminal deoxynucleotidyl transferase with deoxyribonucleotide trisphosphates each comprising a modified base with a photocleavable carbon chain moiety that enables single incorporations when present.

Abstract: The present disclosure relates to oligonucleotide sequences for amplification primers and their use in performing nucleic acid amplifications of HCV, in particular regions that encode the NS3 polypeptide. In some embodiments the primers are used in nested PCR methods for the detection or sequencing of HCV NS3. The oligonucleotide sequences are also provided assembled as kits that can be used to amplify and detect or sequence HCV NS3.

Abstract: A method includes flowing a first fluid through a first channel of a microfluidic apparatus and flowing a second fluid through a second channel of the microfluidic apparatus. The first fluid comprises biological material and a matrix material and is immiscible with the second fluid. The first and second fluids are combined at a junction to form droplets of the first fluid dispersed in the second fluid in a third channel. Multiple exposures of a droplet in the third channel are captured in a single image, comprising: illuminating a region of the third channel with multiple successive illumination pulses during a single frame of the imaging device; identifying the droplet and determining a velocity or a size of the droplet based on an analysis of the captured exposures; and controlling the flow of the first fluid or second fluid to obtain droplets of a target size or velocity.

Abstract: A method of processing a fecal sample from a human subject comprising combining a first portion of a collected fecal sample with a stabilizing buffer that maintains DNA integrity in a fecal sample, and combining a second portion of the sample with a solution that prevents denaturation or degradation of blood proteins found in a fecal sample. Embodiments comprise testing DNA extracted from the first portion of the fecal sample for the presence of a human DNA, and testing the second portion of the fecal sample for the presence of human blood.

Abstract: The invention provides methods for reprogramming somatic cells to generate multipotent or pluripotent cells. Such methods are useful for a variety of purposes, including treating or preventing a medical condition in an individual. The invention further provides methods for identifying an agent that reprograms somatic cells to a less differentiated state.

Abstract: The present disclosure provides compositions and methods for targeted insertion of a gene of interest in the genome of a cell using single-stranded DNA or double-stranded DNA with 3 overhang. Also provided are methods of generating single-stranded DNA or double-stranded DNA with 3? over-hang that can be used for targeted insertion.

Abstract: Methods for constructing consecutively connected copies of nucleic acid molecules are disclosed. Consecutively connected copies of nucleic acid molecules can be used to perform sequencing of the same nucleic acid molecules several times, improving overall accuracy of sequencing. Connected copies of nucleic acid molecules can be constructed by circularizing nucleic acid molecules, performing rolling circle amplification and debranching with nicking and polymerases comprising 5?-3? exonuclease and/or flap endonuclease activity.

Abstract: Compositions of matter comprising RNA silencing molecules capable of mediating cleavage of p21 mRNA are disclosed. Methods of eradicating senescent cells or cancer cells, as well as methods of treating senescence-associated diseases or disorders, cancer, and fibrotic diseases and disorders are also disclosed.

Abstract: The current document discusses electromechanical sequence detectors that transduce changes in the shape of a shape-change sensor component into an electrical signal from which one or more derived values are generated. In a disclosed implementation, the sequence-detection system comprises a mechanical-change sensor that changes shape when specifically interacting with entities within a target, a shape-to-signal-transduction component that transduces changes in the shape of the mechanical-change sensor into an electrical signal, an analysis subsystem that determines the types of entities within the target using the electrical signal, and a control subsystem that continuously monitors operational characteristics of the sequence-detection system and adjusts sequence-detection system operational parameters.

Abstract: Certain disclosed methods include: transmitting an excitation signal into the MUT and transmitting a reference signal to a set of magnitude and phase (M/P) detectors; receiving the response signal; separately comparing a magnitude and phase for each of the excitation signal and the reference signal with corresponding detection ranges for a first one of the M/P detectors; separately comparing a magnitude and phase for each of the response signal and the reference signal with corresponding detection ranges for a second one of the M/P detectors; iteratively adjusting the excitation signal until the response signal has both a magnitude and a phase within the corresponding detection ranges for the second M/P detector; and iteratively adjusting the reference signal until the reference signal has both a magnitude and a phase within the corresponding detection ranges for the first and the second M/P detectors.

Abstract: A composition includes a nanopore including first and second sides and an aperture, nucleotides each including an elongated tag, and a first polynucleotide that is complementary to a second polynucleotide. A polymerase can be disposed adjacent to the first side of the nanopore and configured to add nucleotides to the first polynucleotide based on a sequence of the second polynucleotide. A permanent tether can include a head region anchored to the polymerase, a tail region, and an elongated body disposed therebetween that occurs in the aperture of the nanopore. A first moiety can be disposed on the elongated body that binds to the elongated tag of a first nucleotide upon which the polymerase is acting. A reporter region can be disposed on the elongated body that indicates when the first nucleotide is complementary or is not complementary to a next nucleotide in the sequence of the second polynucleotide.

Abstract: The present invention relates to methods and products for localized or spatial detection and/or analysis of RNA in a tissue sample or a portion thereof, comprising: (a) providing an object substrate on which at least one species of capture probe, comprising a capture domain, is directly or indirectly immobilized such that the probes are oriented to have a free 3? end to enable said probe to function as a reverse transcriptase (RT) primer; (b) contacting said substrate with a tissue sample and allowing RNA of the tissue sample to hybridise to the capture probes; (c) generating cDNA molecules from the captured RNA molecules using said capture probes as RT primers; (d) labelling the cDNA molecules generated in step (c), wherein said labelling step may be contemporaneous with, or subsequent to, said generating step; (e) detecting a signal from the labelled cDNA molecules; and optionally (f) imaging the tissue sample, wherein the tissue sample is imaged before or after step (c).