Abstract: The technology described herein is directed to compositions, sets, and methods for analyzing, detecting, and/or visualizing target molecules. In one aspect, described herein are sets of readout molecules to determine the identity of at least one oligonucleotide tag hybridized to at least one target molecule. In another aspect, described herein are methods of detecting said oligonucleotide tags bound to at least one target molecules using said set of readout molecules.

Abstract: Compositions and methods are provided herein for conducting prime editing of a target DNA molecule (e.g., a genome) that enables the incorporation of a nucleotide change and/or targeted mutagenesis. The compositions include fusion proteins comprising nucleic acid programmable DNA binding proteins (napDNAbp) and a polymerase (e.g., reverse transcriptase), which is guided to a specific DNA sequence by a modified guide RNA, named an PEgRNA. The PEgRNA has been altered (relative to a standard guide RNA) to comprise an extended portion that provides a DNA synthesis template sequence which encodes a single strand DNA flap which is synthesized by the polymerase of the fusion protein and which becomes incoporated into the target DNA molecule.

Abstract: Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AAV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g.

Abstract: The present invention relates to a homogeneous, time resolved, Förster resonance energy transfer (TR-FRET)-based method for detection of SARS-CoV-2, SARS CoV-1, and MERS-CoV antibodies in a patient fluid sample.

Abstract: Compositions and methods are provided herein for conducting prime editing of a target DNA molecule (e.g., a genome) that enables the incorporation of a nucleotide change and/or targeted mutagenesis. The compositions include fusion proteins comprising nucleic acid programmable DNA binding proteins (napDNAbp) and a polymerase (e.g., reverse transcriptase), which is guided to a specific DNA sequence by a modified guide RNA, named an PEgRNA. The PEgRNA has been altered (relative to a standard guide RNA) to comprise an extended portion that provides a DNA synthesis template sequence which encodes a single strand DNA flap which is synthesized by the polymerase of the fusion protein and which becomes incorporated into the target DNA molecule.

Abstract: The present disclosure, at least in part, relates to compositions (e.g., isolated nucleic acid and rAAVs) and methods for treating Non-syndromic hearing loss and deafness (DFNB1) by delivering gap junction beta 2 (GJB2) protein to inner ear cells that normally express GJB2 (e.g., fibrocytes and supporting cells of the organ of Corti and nearby regions). The isolated nucleic acid of the present disclosure comprises an expression cassette, wherein the expression cassette comprises a gap junction beta 2 (GJB2) gene regulatory element (GRE) (e.g., GJB2 enhancers, GJB2 promoters, GJB2 5? UTR, and/or GJB2 3? UTR), and a nucleotide sequence encoding a GJB2 protein.

Abstract: Compositions and methods are provided herein for conducting prime editing of a target DNA molecule (e.g., a genome) that enables the incorporation of a nucleotide change and/or targeted mutagenesis. The compositions include fusion proteins comprising nucleic acid programmable DNA binding proteins (napDNAbp) and a polymerase (e.g., reverse transcriptase), which is guided to a specific DNA sequence by a modified guide RNA, named a PEgRNA. The PEgRNA has been altered (relative to a standard guide RNA) to comprise an extended portion that provides a DNA synthesis template sequence which encodes a single strand DNA flap which is synthesized by the polymerase of the fusion protein and which becomes incorporated into the target DNA molecule.

Abstract: The disclosure provides methods and compositions for treating blood diseases/disorders, such as sickle cell disease, hemochromatosis, hemophilia, and beta-thalassemia. For example the disclosure provides therapeutic guide RNAs that target the promotor of HBG1/2 to generate point mutations that increase expression of fetal hemoglobin. As another example, the disclosure provides therapeutic guide RNAs that target mutations in HBB, Factor VIII, and HFE to treat sickle cell disease, beta-thalassemia, hemophilia and hemochromatosis. The disclosure also provides fusion proteins comprising a Cas9 (e.g., a Cas9 nickase) domain and adenosine deaminases that deaminate adenosine in DNA. In some embodiments, the fusion proteins are in complex with nucleic acids, such as guide RNAs (gRNAs), which target the fusion proteins to a DNA sequence (e.g., an HBG1 or HBG2 protmoter sequence, or an HFE, GBB, or F8 gene sequence).

Abstract: Described herein are engineered microbe-targeting or microbe-binding molecules, kits comprising the same and uses thereof. Some particular embodiments of the microbe-targeting or microbe-binding molecules comprise a carbohydrate recognition domain of mannose-binding lectin, or a fragment thereof, linked to a portion of a Fc region. In some embodiments, the microbe-targeting molecules or microbe-binding molecules can be conjugated to a substrate, e.g., a magnetic microbead, forming a microbe-targeting substrate (e.g., a microbe-targeting magnetic microbead). Such microbe-targeting molecules and/or substrates and the kits comprising the same can bind and/or capture of a microbe and/or microbial matter thereof, and can thus be used in various applications, e.g., diagnosis and/or treatment of an infection caused by microbes such as sepsis in a subject or any environmental surface.

Abstract: Obtain, from an existing machine learning classifier, original probabilistic scores classifying samples taken from two or more groups into two or more classes via supervised machine learning. Associate the original probabilistic scores with a plurality of original Lagrange multipliers. Adjust values of the plurality of original Lagrange multipliers via low-dimensional convex optimization to obtain updated Lagrange multipliers that satisfy fairness constraints as compared to the original Lagrange multipliers. Based on the updated Lagrange multipliers, closed-form transform the original probabilistic scores into transformed probabilistic scores that satisfy the fairness constraints while minimizing loss in utility. The fairness constraints are with respect to the two or more groups.

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: Compositions and methods are provided herein for conducting prime editing of a target DNA molecule (e.g., a genome) that enables the incorporation of a nucleotide change and/or targeted mutagenesis. The compositions include fusion proteins comprising nucleic acid programmable DNA binding proteins (napDNAbp) and a polymerase (e.g., reverse transcriptase), which is guided to a specific DNA sequence by a modified guide RNA, named a PEgRNA. The PEgRNA has been altered (relative to a standard guide RNA) to comprise an extended portion that provides a DNA synthesis template sequence which encodes a single strand DNA flap which is synthesized by the polymerase of the fusion protein and which becomes incoporated into the target DNA molecule.

Abstract: The present invention provides triazolone compounds of general formula (I): in which R1, R2, R3, R4 and R5 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative disorders, as a sole agent or in combination with other active ingredients.

Abstract: The invention provides methods and compositions for reducing tumor-mediated immune evasion and inducing patient-specific immunization.

Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered RNA-targeting systems comprising a novel RNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.

Abstract: Disclosed herein are means for the detection and characterization of neurotoxins such as botulinum neurotoxin (BoNT) or tetanus neurotoxin. The present disclosure provides methods for determining potency and activity of neurotoxins in vitro and in vivo. Also disclosed are polypeptides comprising N- and C-terminal fragments of a reporter protein that are split by a linker comprising a neurotoxin cleavage site. Cleavage of the linker by a neurotoxin decreases reporter protein activity, thereby indicating activity of the neurotoxin. Compositions and kits comprising the disclosed polypeptides, nucleic acids comprising nucleotide sequences encoding such polypeptides, and cells expressing such polypeptides are also disclosed.

Abstract: A radiant cooling device comprises at least one fluidic layer including one or more micro-channel liquid-circuits and at least one structural layer coupled to the at least one fluidic layer. The device further includes a plurality of folds such that the device has a three-dimensional surface geometry having a plurality of inclined surfaces.

Abstract: Compositions and methods are provided for the inhibition of the function of RNA guided endonucleases, including the identification and use of such inhibitors.

Abstract: Provided herein, in some embodiments, are methods and compositions for identifying combinations of transcription factors, for example, those involved in cell type conversion processes, such as cell differentiation.

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.