The present invention relates to methods and compositions for reducing the immunogenicity of chimeric Notch receptors, and specifically to transcription factors useful for controlling gene expression delivered to tissues by such chimeric Notch receptors.

A method for selecting genome edited cells and/or for enrichment of genome edited cells in a population of cells comprising: (a) introducing into a cell or a population of cells at least one first component, at least one second component and at least one third component; and (b) selecting the genome edited cells which transiently express or transiently upregulate a nucleotide sequence encoding a selector.

Compositions, methods, strategies, kits, and systems for the supercharged protein-mediated delivery of functional effector proteins into cells in vivo, ex vivo, or in vitro are provided. Compositions, methods, strategies, kits, and systems for delivery of functional effector proteins using cationic lipids and cationic polymers are also provided. Functional effector proteins include, without limitation, transcriptional modulators (e.g., repressors or activators), recombinases, nucleases (e.g., RNA-programmable nucleases, such as Cas9 proteins; TALE nuclease, and zinc finger nucleases), deaminases, and other gene modifying/editing enzymes. Functional effector proteins include TALE effector proteins, e.g., TALE transcriptional activators and repressors, as well as TALE nucleases. Compositions, methods, strategies, and systems for the delivery of functional effector proteins into cells is useful for therapeutic and research purposes, including, but not limited to, the targeted manipulation of a gene associated with disease, the modulation of the expression level of a gene associated with disease, and the programming of cell fate.

Disclosed are compositions and methods related to the construction and use of universal synthetic notch (synNotch) receptors and chimeric antigen receptor (CAR) T cells.

The present disclosure provides a genetically modified, in vitro immune cell. The immune cell is genetically modified with one or more nucleic acids comprising nucleotide sequences encoding: a) a chimeric polypeptide comprising: i) an antibody specific for a target antigen; and ii) a binding triggered transcriptional activator; and b) a cytokine or proliferation-inducing polypeptide that increases proliferation and/or activity of an effector immune cell, where the nucleotide sequence encoding the cytokine or proliferation-inducing polypeptide is operably linked to a transcriptional control element responsive to the transcriptional activator. The present disclosure provides compositions comprising the genetically modified, in vitro immune cell; and treatment methods comprising administration of the genetically modified, in vitro immune cell.

The present invention provides methods for modulating expression of endogenous cellular genes using recombinant zinc finger proteins.

The application belongs to the field of nucleic acid editing, in particular to the field of clustered regularly interspaced short palindromic repeats (CRISPR) technology. In particular, the application provides a Cas effector protein, a fusion protein with the Cas effector protein, and a nucleic acid molecule encoding the same. Also provided are a compound and a composition for nucleic acid editing (e.g., gene or genome editing) with the protein or the nucleic acid molecule, and a method for nucleic acid editing (e.g., gene or genome editing) using the protein.

The present disclosure generally relates to, inter alia, a new class of receptors engineered to modulate transcriptional regulation in a ligand-dependent manner. Particularly, the new receptors, even though derived from Notch, do not require the Notch negative regulatory regions previously believed to be essential for the functioning of the receptors. In addition, the new receptors described herein incorporate an extracellular oligomerization domain to promote oligomer formation of the chimeric receptors. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various health conditions such as cancers.

Compositions and methods related to Cas proteins, nucleic acids encoding the Cas proteins, and modified host cells comprising the Cas proteins and/or encoding nucleic acids are disclosed. Cas proteins are useful in a variety of applications. Cas proteins bind guide RNAs that in turn provide functional specificity to the Cas proteins, nucleic acids encoding the Cas guide RNAs, and modified host cells comprising the Cas guide RNAs and/or encoding nucleic acids. The Cas polypeptides and corresponding guide RNAs can be used in a variety of applications.

The present disclosure relates to compositions and methods for modulating gene expression and in particular to DNA binding proteins and their use for increasing expression of Klotho. In some examples, the present disclosure provides an isolated or recombinant DNA binding protein comprising or attached to a transcriptional activation domain wherein the DNA binding protein binds to a target sequence within or near a Klotho gene.