The present invention provides compositions and methods for assaying the activity of nicking enzyme and polymerase in a reaction involving the use of a nucleic acid substrate molecule that detects nicking enzyme and polymerase extension activities by the release of a detectable reporter (e.g., a fluorophore).

Engineered CRISPR-Cas9 nucleases with altered and improved PAM specificities and their use in genomic engineering, epigenomic engineering, and genome targeting.

Nucleases and methods of using these nucleases for inserting a sequence encoding a therapeutic α-Gal A protein such as an enzyme into a cell, thereby providing proteins or cell therapeutics for treatment and/or prevention of Fabry disease.

Methods and constructs for RNA-guided targeting of heterologous functional domains such as transcriptional activators to specific genomic loci.

The present disclosure provides AcrIIA7 polypeptides, nucleic acids encoding the AcrIIA7 polypeptides, and kits comprising the AcrIIA7 polypeptides and/or nucleic acids encoding the ACRIIA7 polypeptides. The present disclosure provides methods of inhibiting an activity of a Cas9 polypeptide.

Compositions and methods are provided for variant Cas systems and elements comprising such systems, including, but not limiting to, Cas endonuclease variants, guide polynucleotide/Cas endonuclease complexes comprising Cas endonuclease variants, as well as guide polynucleotides and guide RNA elements that can interact with Cas endonuclease variants. Compositions and methods are provided for genome modification of a target sequence in the genome of a cell. The methods and compositions employ a guide polynucleotide/Cas endonuclease system comprising a Cas9 endonuclease variant to provide an effective system for modifying or altering target sequences within the genome of a cell or organism.

A method of altering a eukaryotic cell is provided including transfecting the eukaryotic cell with a nucleic acid encoding RNA complementary to genomic DNA of the eukaryotic cell, transfecting the eukaryotic cell with a nucleic acid encoding an enzyme that interacts with the RNA and cleaves the genomic DNA in a site specific manner, wherein the cell expresses the RNA and the enzyme, the RNA binds to complementary genomic DNA and the enzyme cleaves the genomic DNA in a site specific manner.

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.

The invention relates to improved alkaline phosphatases, pharmaceutical compositions comprising improved alkaline phosphatases and the use of improved alkaline phosphatases for preventing, treating or curing diseases.

Methods of modulating expression of a target nucleic acid in a cell are provided including use of multiple orthogonal Cas9 proteins to simultaneously and independently regulate corresponding genes or simultaneously and independently edit corresponding genes.