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: Described herein are methods for providing an in vitro intestinal model system, e.g., using primary cells instead of cell lines and/or cancerous cells.

Abstract: The invention provides methods and compositions for inhibiting CD38 activity, and methods of treating or preventing various disorders associated with CD38 activity.

Abstract: The present disclosure provides, in some aspects, nucleic acid nanostructures covalently linked to oligolysine-PEG copolymers.

Abstract: Aspects of the disclosure relate to compositions and methods for targeted protein degradation. In some embodiments, the disclosure relates to methods of evolving protein degrons to interact with certain small molecule inducers (e.g., VS-777, PT-179, or PK-1016). In some embodiments, the disclosure relates to compositions (e.g., peptides, nucleic acids encoding the protein degrons, etc.) used for targeted protein degradation. In some embodiments, the disclosure relates to methods of degrading a target polypeptide in a cell.

Abstract: Systems and methods related to microfluidic devices (e.g., microfluidic devices comprising layers of films) are generally described. In some embodiments, a microfluidic device comprises a substrate configured to facilitate fluid transport, one or more intermediate layers disposed on the substrate, wherein the one or more intermediate layers are configured to define a plurality of fluidly connected microfluidic components, and a top layer disposed on the one or more intermediate layers. In certain embodiments, a microfluidic device comprises a microfluidic channel having a gap or area of increased hydrophobicity in between two separated portions of the channel to separately pin one or more liquids in one or more desired portions of the channel. According to some embodiments, a microfluidic device comprises a microfluidic channel with an inclined surface, such that different portions of the microfluidic channel are associated with different channel heights.

Abstract: Provided herein are compounds of Formula (I-A), (I-B), or (I-C), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically enriched forms, prodrugs, or mixtures thereof, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing diseases and/or conditions (e.g., neurological disease (e.g., Alzheimer's disease, multiple sclerosis, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis), metabolic disorder (e.g., obesity, diabetes, X-linked adrenoleukodystrophy (X-ALD)), proliferative disease (e.g., cancers), hepatic disease (e.g., liver cirrhosis), conditions associated with autophagy (e.g., neurodegenerative disease, infection, cancer, conditions associated with aging, heart disease), conditions associated with aging, conditions associated with modulating the mPTP, cardiovascular conditions (e.g.

Abstract: Disclosed herein are semiconductor devices to provide a CMOS-compatible, wafer-scale, multi-well platform that can be used for biomedical or other applications, and methods to operate the same. In some embodiments, circuitry is provided underneath a multiple-well array to electrically interface with electrodes in the wells. To interface with electrodes in a large array, circuitry may be fabricated on a single silicon (Si) wafer having a dimension that is at least the same or larger than that of the multiple-well array. According to one aspect of the present disclosure, standard CMOS fabrication process such as those known to be used in a standard semiconductor foundry may be used without expensive customization for complex fabrication procedures. This may help the production cost to be lowered in some cases.

Abstract: Described herein are methods and uses thereof for in vivo evaluating functions of multiple genes in parallel by combining in utero genetic perturbation of progenitor cells and single-cell transcriptomic profiling of progeny cells in animals. These methods can be used, among other things, to reveal in vivo gene functions in a cell type-specific manner.

Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA. Methods for making and using and uses of such systems, methods, and compositions and products from such methods and uses are also disclosed and claimed.

Abstract: Methods of selectively sequencing amplicons in a biological sample are provided.

Abstract: Low loss fiber-to-chip interfaces for lithium niobate photonic integrated circuits are provided. An optical circuit includes a waveguide comprising an electro-optical material. The waveguide includes an elevated ridge and a slab underlying the elevated ridge, the elevated ridge and the slab extending along a central axis toward an optical interface. The elevated ridge and the slab each have a plurality of cross-sections along the central axis, each cross-section having a width measured perpendicular to the central axis, wherein the width of elevated ridge is smaller than the width of the slab for every cross-section along the central axis. The elevated ridge includes a tapered portion having a first taper, wherein the cross-section of the elevated portion decreases along the central axis toward the optical interface. The slab includes a tapered portion having a second taper, wherein the cross-section of the slab decreases along the central axis toward the optical interface.

Abstract: A nonvolatile memory device includes a resistance switching layer, a gate on the resistance switching layer, a gate oxide layer between the resistance switching layer and the gate, and a source and a drain, spaced apart from each other, on the resistance switching layer. A resistance value of the resistance switching layer is changed based on an illumination of light irradiated onto the resistance switching layer and is maintained as a changed resistance value.

Abstract: This invention provides methods of using phagocytic cells in the diagnosis, prognosis, or monitoring of diseases or conditions. The invention also provides methods of using phagocytic cells to identify markers of diseases or conditions.

Abstract: The present disclosure provides Cas protein variants comprising one or more amino acid substitutions relative to wild-type Cas14a1. Fusion proteins comprising the Cas protein variants described herein are also provided by the present disclosure. Further provided herein are methods for modifying a target nucleic acid using the Cas proteins and fusion proteins provided herein. The present disclosure also provides guide RNAs, complexes, polynucleotides, systems, cells, kits, and pharmaceutical compositions.

Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues of organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provide dare methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems.

Abstract: The present invention is based, in part, on the discovery of monoclonal and polyclonal antibodies that specifically bind to phosphorylated PD-1, as well as immunoglobulins, polypeptides, nucleic acids thereof, and methods of using such antibodies for diagnostic, prognostic, and therapeutic purposes.

Abstract: The present invention provides stapled polypeptides of the Formulae (I) and (VI): and salts thereof; wherein the groups ; R1a, R1b, R1c, R2a, R3a, R2b, R3b, R4a, R4b, RA, RZ, L1a, L1b, L2, L3, XAA, v, w, p, m, s, n, t, and q are as defined herein. The present invention further provides methods of preparing the inventive stapled polypeptides from unstapled polypeptide precursors. The present invention further provides pharmaceutical compositions comprising a stapled polypeptide of Formula (I) or (VI), and methods of using the stapled peptides. The present invention also provides modifications of the staples post ring closing metathesis.

Abstract: Disclosed herein are compositions and methods for labeling cells using click chemistry reagents. The compositions and methods disclosed herein provide a specific and efficient means of localizing desired agents to a variety of cell types in vivo and in vitro.