Abstract: The subject matter disclosed herein is generally directed to CD8+ tumor infiltrating lymphocytes comprising gene signatures associated with response to immunotherapy treatment. Moreover, the subject matter disclosed herein is generally directed to methods and compositions for use of the gene signatures. Specifically, disclosed herein are gene signatures associated with response to checkpoint blockade therapy and immune cell subtypes characterized by said gene signatures. Further disclosed are methods of using said gene signatures and immune cell subtypes. Further disclosed are pharmaceutical compositions comprising populations of CD8+ TILs enriched for a specific subtype.

Abstract: An atlas of intestinal epithelial cells, intestinal epithelial stem cells and intestinal immune cells identifies new cell populations, markers, networks, and responses to stimuli. Intestinal T cells drive intestinal epithelial cell differentiation and activity. Accordingly, disclosed are methods of modulating intestinal epithelial cell differentiation, maintenance and/or function, related methods for the treatment of disease, including IBD. Also disclosed are methods and kits for identifying cell types, their differentiation, homeostasis and activation.

Abstract: The present invention relates to compounds of formula (I) processes for their production and their use as pharmaceuticals. The compounds are inhibitors of Casein kinase 1 alpha and/or delta (CSNK1? and/or ?) useful for the treatment of proliferative disorders.

Abstract: The present inventions generally relate to site-specific delivery of nucleic acid modifiers and includes novel DNA-binding proteins and effectors that can be rapidly programmed to make site-specific DNA modifications. The present inventions also provide a synthetic all-in-one genome editor (SAGE) systems comprising designer DNA sequence readers and a set of small molecules that induce double-strand breaks, enhance cellular permeability, inhibit NHEJ and activate HDR, as well as methods of using and delivering such systems.

Abstract: The present invention provides for methods to obtain multiple information-rich samples at different time points from the same cell while minimally disrupting the cell. The subject matter disclosed herein is generally related to nucleic acid constructs for continuous monitoring of live cells. Specifically, the subject matter disclosed herein is directed to nucleic acid constructs that encode a fusion protein and a construct RNA sequence that induce live cells to self-report cellular contents while maintaining cell viability. The present invention may be used to monitor gene expression in single cells while maintaining cell viability.

Abstract: The invention provides for systems, methods, and compositions for targeting and editing nucleic acids. In particular, the invention provides non-naturally occurring or engineered RNA-targeting systems comprising a RNA-targeting Cas13 protein, at least one guide molecule, and at least one adenosine deaminase protein or catalytic domain thereof.

Abstract: Techniques Nuc-seq, Div-Seq, and Dronc-Seq are allow for unbiased analysis of any complex tissue. Nuc-Seq, a scalable single nucleus RNA-Seq method, can sensitively identify closely related cell types, including within the adult hippocampus. Div-seq combines Nuc-Seq with EdU-mediated labeling of proliferating cells, allowing tracking of transcriptional dynamics of newborn neurons in an adult neurogenic region in the hippocampus. Dronc-Seq uses a microfluidic device to co-encapsulate individual nuclei in reverse emulsion aqueous droplets in an oil medium together with one uniquely barcoded mRNA-capture bead.

Abstract: The invention provides for systems, methods, and compositions for targeting RNA. In particular, the invention provides a non-naturally occurring or engineered RNA-targeting system comprising an RNA-targeting Cas protein and at least one RNA-targeting guide RNA, wherein said RNA-targeting guide RNA is capable of hybridizing with a target RNA in a cell.

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

Abstract: Disclosed herein are compositions, methods, kits, and systems relating to efficient delivery of cargos (e.g., therapeutic cargos) into cells, for instance, for in vivo delivery. The present disclosure provides lipid-containing particles (e.g., virus-like particles) for delivering therapeutic cargos. The present disclosure also provides polynucleotides encoding the lipid-containing particles provided herein, which may be useful for producing said lipid-containing particles. Also provided are methods for editing nucleic acid molecules in cells using the lipid-containing particles provided herein, as well as cells and kits comprising the lipid-containing particles.

Abstract: The present disclosure relates to methods aimed towards non-invasive targeted genomic and epigenomic sequencing of spatially-defined cellular or subcellular region. More particularly, the present disclosure relates to methods of using photoselection to achieve non-invasive targeted genomic and epigenomic sequencing of spatially-defined cellular or subcellular regions, via the use of light-activated probes.

Abstract: The present invention relates to a method for generating primers and/or probes for use in analyzing a sample which may comprise a pathogen target sequence comprising providing a set of input genomic sequence to one or more target pathogens, generating a set of target sequences from the set of input genomic sequences, identifying one or more highly conserved target sequences, and generating one or more primers, one or more probes, or a primer pair and probe combination based on the one or more conserved target sequences.

Abstract: The disclosure includes zinc prodrugs for targeted delivery of therapeutic, diagnostic or imaging agents to ?-cells and methods of use therefor. The disclosure also includes targeted delivery of small molecules to ?-cells that stabilize and activate CRISPR effector proteins comprising at least one destabilization domain, to enable CRISPR-based genome editing and transcriptional activation or repression in ?-cells.

Abstract: The present disclosure provides Cas9 variants, and base editors comprising these variants, that recognize non-canonical protospacer adjacent motifs (PAMs) and have less restrictive PAM requirements for editing. The present disclosure provides Cas9 protein variants comprising one or more amino acid substitutions relative to wild-type Nme2Cas9. Fusion proteins comprising the Cas protein variants described herein are also provided by the present disclosure. Further provided herein are methods for editing a target nucleic acid using the Cas variants and fusion proteins provided herein. The present disclosure also provides guide RNAs, complexes, polynucleotides, cells, kits, and pharmaceutical compositions. Further described herein are phage-assisted continuous evolution (PACE) systems, vectors, methods, and devices.

Abstract: Provided herein is a nucleic acid detection system comprising: a CRISPR system comprising an effector protein and one or more guide RNAs designed to bind to corresponding target molecules; an RNA-based masking construct; and optionally, nucleic acid amplification reagents to amplify target RNA molecules in a sample. In another aspect, the embodiments provide a polypeptide detection system comprising: a CRISPR system comprising an effector protein and one or more guide RNAs designed to bind a trigger RNA, an RNA-based masking construct; and one or more detection aptamers comprising a masked RNA polymerase promoter binding site or a masked primer binding site. In some embodiments, the system may be used to detect viruses in samples.

Abstract: RNA editing tools for use in systems designed to measure RNA in vivo and manipulate specific cell types are disclosed herein. An RNA sensor system comprising a) a single-stranded RNA (ssRNA) sensor comprising a stop codon and a payload; optionally wherein the ssRNA sensor further comprises a normalizing gene; and b) an adenosine deaminase acting on RNA (ADAR) deaminase; wherein the sensor is capable of binding to a ssRNA target to form a double-stranded RNA (dsRNA) duplex that becomes a substrate for the ADAR deaminase; wherein the substrate comprises a mispairing within the stop codon; and wherein the mispairing is editable by the ADAR deaminase, which editing can effectively remove the stop codon so as to enable translation and expression of the payload. A method of quantifying ribonucleic acid (RNA) levels using the RNA sensor system is also disclosed.

Abstract: Described herein are engineered antigen presenting cells that can be capable of modulating a target T-cell in a T-cell antigen specific manner. In some embodiments, the engineered APCs can include a modified antigen presentation pathway. Also described herein are methods of making and using the engineered antigen presenting cells.

Abstract: The subject matter disclosed herein is generally directed to tissue specific modulation of Th17 differentiation and pathogenicity by targeting tissue specific Th17 gene programs and gene targets. The tissue specific modulation may be used therapeutically to treat a disease or condition in the tissue where it arises. The subject matter disclosed herein is also directed to detecting tissue specific Th17 cells for diagnostic and therapeutic methods.

Abstract: Methods and compositions for a single- or multi-pot protocol for the efficient end to end capture of RNAs (inclusive of their poly-A tail or their 3? end) is described. Capture oligonucleotides containing a 3? non-extendable end and a selectively cleavable base upstream of an oligo-dT or oligo-dN and a 5? sequence containing unique molecular identifiers, and 2) a deoxyuracil glycosylase that acts only on a deoxyuracil present in a DNA: DNA duplex or DNA/RNA heteroduplex are used. A dual template switching mechanism may be used.

Abstract: The specification provides programmable base editors that are capable of introducing a nucleotide change and/or which could alter or modify the nucleotide sequence at a target site in mitochondrial DNA (mtDNA) with high specificity and efficiency. Moreover, the disclosure provides fusion proteins and compositions comprising a programmable DNA binding protein (e.g., a mitoTALE, a mitoZFP, or a CRISPR/Casp) and double-stranded DNA deaminase that is capable of being delivered to the mitochondria and carrying out precise installation of nucleotide changes in the mtDNA. The fusion proteins and compositions are not limited for use with mtDNA, but also may be used for base editing of any double-stranded target DNA.