Disclosed herein are methods and compositions for insertion of transgene sequences encoding proteins involved in clotting into the genome of a cell for treating conditions including hemophilias.

Methods and compositions for controlling gene expression are disclosed.

Disclosed herein are engineered cleavage half-domains; fusion polypeptides comprising these engineered cleavage half-domains; polynucleotides encoding the engineered cleavage half-domains and fusion proteins; and cells comprising said polynucleotides and/or fusion proteins. Also described are methods of using these polypeptides and polynucleotides, for example for targeted cleavage of a genomic sequence.

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

A nucleic acid constructs are used in improving site-specific insertion of an exogenous nucleic acid into a genome. In some aspects the nucleic acid construct having a first polynucleotide sequence encoding a DNA binding protein engineered to bind to a specific genomic DNA sequence, a second polynucleotide having a modified integrase or a modified transposase that enables insertion of exogenous nucleic acid into the genome, and a nucleic acid sequence encoding a linker between the two nucleotides. In some aspects, the nucleic acid construct encodes a fusion protein, for example, a fusion protein for delivery to a cell by a lentiviral particle.

The present invention provides RNA-guided endonucleases, which are engineered for expression in eukaryotic cells or embryos, and methods of using the RNA-guided endonuclease for targeted genome modification in in eukaryotic cells or embryos. Also provided are fusion proteins, wherein each fusion protein comprises a CRISPR/Cas-like protein or fragment thereof and an effector domain. The effector domain can be a cleavage domain, an epigenetic modification domain, a transcriptional activation domain, or a transcriptional repressor domain. Also provided are methods for using the fusion proteins to modify a chromosomal sequence or regulate expression of a chromosomal sequence.

The present disclosure provides tissue-specific Wnt signal enhancing molecules, and related methods of using these molecules to increase Wnt signaling in liver tissues.

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.

Disclosed herein are Htt repressors and methods and compositions for use of these Htt repressors.

Compositions and methods are provided for integrating one or more genes of interest into cellular DNA without substantially disrupting the expression of the gene at the locus of integration, i.e., the target locus. These compositions and methods are useful in any in vitro or in vivo application in which it is desirable to express a gene of interest in the same spatially and temporally restricted pattern as that of a gene at a target locus while maintaining the expression of the gene at the target locus, for example, to treat disease, in the production of genetically modified organisms in agriculture, in the large scale production of proteins by cells for therapeutic, diagnostic, or research purposes, in the induction of iPS cells for therapeutic, diagnostic, or research purposes, in biological research, etc. Reagents, devices and kits thereof that find use in practicing the subject methods are also provided.