Abstract: Disclosed herein are methods and compositions for targeted cleavage of a genomic sequence, targeted alteration of a genomic sequence, and targeted recombination between a genomic region and an exogenous polynucleotide homologous to the genomic region. The compositions include fusion proteins comprising a cleavage domain (or cleavage half-domain) and an engineered zinc finger domain, as well as polynucleotides encoding same. Fusion proteins comprising cleavage half-domains are used in pairs, to reconstitute a functional cleavage domain. In these fusion proteins, the zinc finger domain can be N-terminal to the cleavage half-domain, or the cleavage half-domain can be N-terminal to the zinc finger domain.

Abstract: Disclosed herein are modified plant zinc finger proteins; compositions comprising modified plant zinc finger proteins and methods of making and using modified plant zinc finger proteins. The modified plant zinc finger proteins, in contrast to naturally-occurring plant zinc finger proteins, have a binding specificity that is determined by tandem arrays of modular zinc finger binding units.

Abstract: A variety of zinc finger proteins (ZFPs) and methods utilizing such proteins are provided for use in treating neuropathic pain. ZFPs that bind to a target site in genes that are aberrantly expressed in subjects having neuropathic pain are described. In addition, ZFPs that bind to a target site in genes expressed at normal levels in subjects experiencing neuropathic pain, modulation of whose expression results in decreased pain perception, are also provided. For example, genes that are over-expressed in the dorsal root ganglia (DRG) of pain patients (e.g., VR1, TRKA and/or Nav1.8) can be repressed, whereas genes that are under-expressed in the same populations can be activated.

Abstract: The present invention provides methods of regulating gene expression using recombinant zinc finger proteins, for functional genomics and target validation applications.

Abstract: Disclosed herein are methods and compositions for modulating expression of endogenous cellular genes using recombinant zinc finger proteins.

Abstract: Methods and compositions for the identification, isolation and characterization of regulatory DNA sequences in a cell of interest are provided. Also provided are libraries of regulatory sequences obtained according to the methods, and databases comprising collections of regulatory sequences for a particular cell of interest. In addition, various uses for the regulatory sequences so obtained, and uses for the databases of regulatory sequences, are provided. Also disclosed are computer systems and computer program products for utilizing the databases to conduct various genetic analyses, and uses of accessible regulatory sequences in the design of vectors bearing transgenes.

Abstract: Provided herein are a variety of methods and compositions for regulating angiogenesis, such methods and compositions being useful in a variety of applications where modulation of vascular formation is useful, including, but not limited to, treatments for ischemia and wound healing. Certain of the methods and compositions accomplish this by using various zinc finger proteins that bind to particular target sites in one or more VEGF genes. Nucleic acids encoding the zinc finger proteins are also disclosed. Methods for modulating the expression of one or more VEGF genes with the zinc finger proteins and nucleic acids are also disclosed. Such methods can also be utilized in a variety of therapeutic applications that involve the regulation of endothelial cell growth. Pharmaceutical compositions including the zinc finger proteins or nucleic acids encoding them are also provided.

Abstract: The invention provides criteria and methods for selecting optimum subsequence(s) from a target gene for targeting by a zinc finger protein. Some of the methods of target site selection seek to identify one or more target segments having a DNA motif containing one or more so-called D-able subsites having the sequence 5?NNGK3?. Other methods of the invention are directed to selection of target segments within target genes using a correspondence regime between different triplets of three bases and the three possible positions of a triplet within a nine-base site. In another aspect, the invention provides methods of designing zinc finger proteins that bind to a preselected target site. These methods can be used following the preselection of target sites according to the procedures and criteria described above. The methods of design use a database containing information about previously characterized zinc finger proteins.

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

Abstract: The present invention relates to methods of using libraries of randomized zinc finger proteins to identify genes associated with selected phenotypes.

Abstract: Disclosed herein are compositions and method comprising non-canonical (e.g., non-C2H2) zinc finger proteins.

Abstract: Disclosed herein are compositions and method comprising non-canonical (e.g., non-C2H2) zinc finger proteins.

Abstract: Methods for assessing potential pharmacological effects and/or side effects of an agent, based on the effect of the agent on the distribution and properties of accessible regions in cellular chromatin, are provided.

Abstract: The present invention relates to methods of using libraries of randomized zinc finger proteins to identify genes associated with selected phenotypes.

Abstract: Disclosed herein are compositions comprising an engineered zinc finger protein and a nuclear hormone receptor transcriptional control domain, polynucleotides encoding one or more components of the compositions, methods of making the compositions and methods of using these compositions, for example to modulate gene expression and/or to generate transgenic plants or animals.

Abstract: Provided herein are a variety of methods and compositions for regulating angiogenesis, such methods and compositions being useful in a variety of applications where modulation of vascular formation is useful, including, but not limited to, treatments for ischemia and wound healing. Certain of the methods and compositions accomplish this by using various zinc finger proteins that bind to particular target sites in one or more VEGF genes. Nucleic acids encoding the zinc finger proteins are also disclosed. Methods for modulating the expression of one or more VEGF genes with the zinc finger proteins and nucleic acids are also disclosed. Such methods can also be utilized in a variety of therapeutic applications that involve the regulation of endothelial cell growth. Pharmaceutical compositions including the zinc finger proteins or nucleic acids encoding them are also provided.

Abstract: Methods and compositions for dedifferentiating nuclei from somatic cells are provided. Such methods and compositions are useful for facilitating processes such as, for example, cloning and immortalization of cells.

Abstract: Disclosed herein are compositions and method useful in screening a compound for its interaction and/or effect with a molecular target and/or cellular process.

Abstract: The specificity of binding of a zinc finger to a triplet or quadruplet nucleotide target subsite depends upon the location of the zinc finger in a multifinger protein and, hence, upon the location of its target subsite within a larger target sequence. The present disclosure provides zinc finger amino acid sequences for recognition of triplet target subsites having the nucleotide G in the 5?-most position of the subsite, that have been optimized with respect to the location of the subsite within the target site. Accordingly, the disclosure provides finger position-specific amino acid sequences for the recognition of GNN target subsites. This allows the construction of multi-finger zinc finger proteins with improved affinity and specificity for their target sequences, as well as enhanced biological activity.

Abstract: Provided herein are a variety of methods and compositions for regulating angiogenesis, such methods and compositions being useful in a variety of applications where modulation of vascular formation is useful, including, but not limited to, treatments for ischemia and wound healing. Certain of the methods and compositions accomplish this by using various zinc finger proteins that bind to particular target sites in one or more VEGF genes. Nucleic acids encoding the zinc finger proteins are also disclosed. Methods for modulating the expression of one or more VEGF genes with the zinc finger proteins and nucleic acids are also disclosed. Such methods can also be utilized in a variety of therapeutic applications that involve the regulation of endothelial cell growth. Pharmaceutical compositions including the zinc finger proteins or nucleic acids encoding them are also provided.