Abstract: The present disclosure provides compositions and methods for enhanced healing of wounds, e.g. cutaneous wounds, by application of a scaffold or matrix, e.g. a hydrogel, comprising an effective dose of edited dendritic cells (DCs). As used herein, edited dendritic cells refers to mammalian, usually human, dendritic cells that have been genetically modified to alter expression of one or more genes involved in wound healing. In some embodiments edited DC are modified to downregulate or substantially eliminate expression of N-myc downregulated gene 2 (Ndrg2) expression, which cells may be referred to as Ndrg2 KO DCs.

Abstract: Provided herein are valency controllable receptor polypeptides configured to oligomerize upon recognition of a custom input. The receptors include an extramembrane signal recognition domain configured to recognize an extramembrane signal different from the custom input, a valency control module configured to recognize the custom input and induce oligomerization of the polypeptide, and an intramembrane signaling domain configured to modulate one or more intramembrane pathways. The provided receptors are particularly useful for engineered cell therapies. Also provided are systems and host cells including the disclosed receptors, and methods for using the disclosed materials.

Abstract: The present disclosure provides one or more engineered nucleases and systems, compositions, and methods thereof, wherein the one or more engineered nucleases can be used to effect binding, cleaving, and/or editing a target polynucleotide sequence. The one or more engineered nucleases can be engineered variants of a small CRISPR/Cas protein.

Abstract: The present disclosure provides one or more engineered nucleases and systems, compositions, and methods thereof, wherein the one or more engineered nucleases can be used to effect binding, cleaving, and/or editing a target polynucleotide sequence. The one or more engineered nucleases can be engineered variants of a small CRISPR/Cas protein.

Abstract: The disclosure provides compositions, methods, and systems for modulating expression of target genes (e.g., target endogenous genes). Complexes of the disclosure can be useful for bringing one or more heterologous gene effectors into close proximity with a target gene or target gene regulatory sequence, thereby facilitating modulation of an expression or activity level of the target gene. The disclosure provides, for example, compositions, systems, and methods for high throughput screens to identify heterologous gene effector domains and complexes of the effector domains with guide moieties to modulate expression of particular target gene(s). The disclosure also provides complexes identified by systems disclosed herein that can be employed for other purposes, such as research or as therapeutics.

Abstract: The present disclosure generally relates to engineered Cluster Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated (Cas) 12a proteins and system, and methods for use in gene editing and gene modulation for application to gene therapy. Related systems and methods of gene modulation are also disclosed.

Abstract: The present disclosure generally relates to compositions and methods simultaneous, multi-mode gene expression regulation (e.g., simultaneous upregulation and down regulation of multiple target genes). The present disclosure further relates to novel constructs for engineered multiplex CRISPR arrays.

Abstract: The present disclosure provides systems, compositions and methods for regulating expression of a target polynucleotide in a cell. The systems, compositions and methods comprise a chimeric receptor polypeptide comprising a G-protein coupled receptor (GPCR) or a fragment thereof, a chimeric adaptor polypeptide, at least one actuator moiety and a cleavage moiety.

Abstract: The present disclosure provides one or more engineered nucleases and systems, compositions, and methods thereof, wherein the one or more engineered nucleases can be used to effect binding, cleaving, and/or editing a target polynucleotide sequence. The one or more engineered nucleases can be engineered variants of a small CRISPR/Cas protein.

Abstract: The present disclosure provides compositions, systems, and methods for genome editing, efficient knock-in of large DNA fragments, and long-term, stable, high expression of integrated transgenes. Also provided are modified cells, vaccines comprising modified cells, and methods of using such cells to induce an immune response.

Abstract: Provided herein are chimeric transmembrane receptor polypeptides configured to oligomerize upon recognition of an extramembrane signal. The receptors include an extramembrane domain, a transmembrane domain, and an intramembrane domain configured to induce activation of one or more intramembrane signal pathways upon oligomerization of the receptor. The provided receptors are particularly useful for engineered cell therapies. Also provided are systems and host cells including the disclosed receptors, and methods for using the disclosed materials.

Abstract: The present disclosure provides systems for immune cell regulation and methods of immunotherapy. Systems of the present disclosure for immune cell regulation comprise a chimeric receptor polypeptide, a chimeric adaptor polypeptide, a gene modulating polypeptide (GMP), and a cleavage moiety.

Abstract: Provided herein are Cas proteins and guide RNA molecules engineered to exhibit increased activity in eukaryotic cells. The provided Cas proteins and RNA molecules are particularly useful for applications where modulation of eukaryotic nucleic acids with relatively small molecules is advantageous. Also provided are nucleic acids and vectors encoding the disclosed Cas proteins and guide RNA molecules, pharmaceutical compositions including the Cas proteins and guide RNA molecules, and methods for using the disclosed materials.

Abstract: The present disclosure provides systems, compositions and methods for regulating expression of a target polynucleotide in a cell. The systems, compositions and methods comprise a chimeric receptor polypeptide comprising a G-protein coupled receptor (GPCR) or a fragment thereof, a chimeric adaptor polypeptide, at least one actuator moiety and a cleavage moiety.

Abstract: Fusion constructs encoding RNase-H-like domain containing compositions are disclosed. Disclosed are also compositions and methods utilizing RNase-H-like domain containing compositions for the treatment of cancer. Also disclosed are the methods of making and using the RNase-H-like domain containing compositions in treating various diseases, conditions, and cancer.

Abstract: Described herein are systems for targeting viral genomes. Also described herein are methods for targeting viral genomes utilizing the systems described in the instant disclosure. In some cases, systems and methods disclosed herein can be used to treat viral infections. In preferred embodiments, the systems utilise a CRISPR/Cas13d complex to target the genome of an RNA virus such as coronavirus or influenza virus.

Abstract: Methods, compositions, and kits are provided for CRISPR/Cas mediated transcriptional modulation.

Abstract: Fusion constructs encoding RNase-H-like domain containing compositions are disclosed. Disclosed are also compositions and methods utilizing RNase-H-like domain containing compositions for the treatment of cancer. Also disclosed are the methods of making and using the RNase-H-like domain containing compositions in treating various diseases, conditions, and cancer.

Abstract: Provided herein are compositions and methods for identifying and using stem cell regulation factors. For example, in some embodiments, provided herein are compositions and methods for identifying stem cell regulation factors using marker gene expression libraries. Also provided herein are compositions and methods for generating differentiated cells lines and uses of such cell lines.

Abstract: Constructs comprising Argonautes and neighboring genes are disclosed for use in gene editing. Disclosed are also compositions and methods utilizing these Argonautes and neighboring genes. Also disclosed are the methods of making and using the Argonautes and neighboring genes in treating various diseases, conditions, and cancer.