Abstract: Compositions and methods for inducing and isolating virus-like particles (VLPs), and for allowing real-time assessment of VLP-captured analytes obtained from targeted living mammalian cells, are provided.

Abstract: The present disclosure relates to compositions and methods for combinatorial assessment of nanoscale droplets, as specifically exemplified by massively parallel assessment of spatially-directed (while agnostic as to precise droplet content) combinations of droplets harboring distinct and independently identifiable microbial types and/or chemical compounds or mixtures. More particularly, the disclosure relates to a platform and methodologies for identifying advantageous (including synergistic, additive, etc.) microbial interactions and/or chemical compound or mixture interactions with microbes in a manner that allows for binary, trinary, etc. combinatorial assessments to be performed across a range of many discrete input types of microbes (e.g., 6-16 or more discrete input microbial types), to an extent capable of approaching comprehensive sampling and measurement of microbial community combinations from a selected panel of microbial inputs, optionally also in the presence of chemical compounds or mixtures (e.

Abstract: Described herein are non-Class I engineered CRISPR-Cas systems and components thereof, formulations thereof, cells thereof, and organisms thereof. Methods of making and using the CRISPR-Cas system described herein.

Abstract: The present application provides systems, methods and compositions used for targeted gene modification, targeted insertion, perturbation of gene transcripts, nucleic acid editing. Novel nucleic acid targeting systems comprise components of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) systems and transposable elements.

Abstract: Provided herein are compounds useful for the treatment of various parasitic diseases. These compounds, as well as pharmaceutically acceptable salts thereof may be formulated in pharmaceutical compositions, veterinary compositions and may be used in methods of treatment and/or prophylaxis of diseases spread by parasites, including cryptosporidiosis.

Abstract: Provided are therapeutic virus vectors, particularly, recombinant adeno-associated virus (rAAV) vectors, designed to contain an enhancer sequence that specifically restricts expression of an effector gene (e.g., an SCN1A-encoding polynucleotide, Gq-DREADD-encoding polynucleotide, or PSAM-encoding polynucleotide) contained in the vector to PV-expressing GABAergic interneuron or to neuron cell populations in the brain. The rAAV vectors, compositions and methods thereof are useful for treating subjects afflicted with neuropathologies, seizures, pharmacologically-intractable forms of epilepsy including Dravet syndrome (DS), a form of infantile epilepsy associated with severe seizures, cognitive impairment and premature death, as the cause of DS involves loss of function of a sodium channel encoded by the SCN1A gene.

Abstract: The present disclosure relates to compositions and methods for assessing extended length T-cell receptor (TCR) transcript sequences (i.e., TCR transcript sequences that span TCR transcript variable regions) in a spatially-defined manner across a tissue sample, specifically providing for obtaining useful TCR sequences at high spatial resolution while also assessing relative macromolecule abundance (e.g., RNA expression levels) with deep transcriptomic coverage at similarly high-resolution across the tissue sample.

Abstract: The present application provides systems, methods and compositions used for targeted gene modification, targeted insertion, perturbation of gene transcripts, and nucleic acid editing. Novel nucleic acid targeting systems comprise components of Type VII Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) systems and transposable elements.

Abstract: Embodiments disclosed herein are directed to engineered CRISPR-Cas effector proteins that comprise at least one modification compared to an unmodified CRISPR-Cas effector protein that enhances binding of the of the CRISPR complex to the binding site and/or alters editing preference as compared to wild type. In certain example embodiments, the CRISPR-Cas effector protein is a Type V effector protein. In certain other example embodiments, the Type V effector protein is Cpf1. Embodiments disclosed herein are directed to viral vectors for delivery of CRISPR-Cas effector proteins, including Cpf1. In certain example embodiments, the vectors are designed so as to allow packaging of the CRISPR-Cas effector protein within a single vector. There is also an increased interest in the design of compact promoters for packing and thus expressing larger transgenes for targeted delivery and tissue-specificity.

Abstract: The present disclosure provides compositions and methods for performance of targeted mutagenesis in higher eukaryotic cells, e.g., mammalian cells, across large stretches of targeted sequence. Compositions and methods that rely upon combination of a bacteriophage polymerase with a nucleic acid-editing deaminase to achieve robust mutagenesis of targeted regions of nucleic acid sequence under control of a phage promoter are specifically provided.

Abstract: Provided herein are compounds useful for the treatment of various parasitic diseases. These compounds, as well as pharmaceutically acceptable salts thereof may be formulated in pharmaceutical compostions, veterinary compositions and may be used in methods of treatment and/or prophylaxis of diseases spread by parasites, including malaria and cryptosporidiosis.

Abstract: The present invention relates to DNA microscopy methods to record the cellular co-localization and/or spatial distributions of arbitrary nucleic acid sequences, or other biomolecules tagged with nucleic sequences. The method involves sequence-components which may identify the targeted sequences-of-interest themselves and/or spatial beacons relative to which their distances are measured.

Abstract: Systems and methods for rapid diagnostics related to the use of CRISPR effector systems and optimized guide sequences, including multiplex lateral flow diagnostic devices and methods of use, are provided.

Abstract: Embodiments of the disclosure include compositions and methods for treating diseases (e.g., brain diseases) using genetic engineered cells. In some cases, the cells are engineered hematopoietic stem cells (HSCs), which are capable of engrafting to a central nervous system and differentiating to progeny cells (e.g., microglial cells).

Abstract: The present invention generally relates to methods and compositions used delivery of gene editing compositions including transcriptional effectors with parvovirus and preferred methods for making same.

Abstract: Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of malaria.

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 and prophylaxis of diseases, in particular hyperproliferative disorders, as a sole agent or in combination with other active ingredients.

Abstract: The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of microsatellite unstable cancers. In particular, the instant disclosure provides for identification of a cancer as exhibiting microsatellite instability (MSI) and/or impaired mismatch repair (MMR), and selection and/or administration of an inhibitor of the WRN helicase as a therapeutic agent for such a cancer and/or subject having or at risk of developing such a cancer.

Abstract: The invention relates to methods of altering expression of a genomic locus of interest or specifically targeting a genomic locus of interest in an animal cell, which may involve contacting the genomic locus with a non-naturally occurring or engineered composition that includes a deoxyribonucleic acid (DNA) binding polypeptide having a N-terminal capping region, a DNA binding domain comprising at least five or more Transcription activator-like effector (TALE) monomers and at least one or more half-monomers specifically ordered to target the genomic locus of interest, and a C-terminal capping region, wherein the polypeptide includes at least one or more effector domains, and wherein the polypeptide is encoded by and translated from a codon optimized nucleic acid molecule so that the polypeptide preferentially binds to the DNA of the genomic locus.

Abstract: The present disclosure provides compositions and methods capable of potentiating the effects of antibiotics against bacterial infections that either have developed, or that possess the potential to develop, antibiotic tolerance. Methods of sensitizing antibiotic tolerant bacteria to antibiotics, as well as pharmaceutical compositions and therapeutic/prophylactic methods directed at antibiotic tolerant bacteria are also provided.