Altius Institute for Biomedical Sciences

University of Washington

Sangamo Therapeutics, Inc.

Memorial Sloan Kettering Cancer Center

John A Stamatoyannopoulos

Shreeram Akilesh

William Sean Kerwin

Fyodor Urnov

George Stamatoyannopoulos

Alexander Muratov

Wouter Meuleman

Vivek Nandakumar

Andreas Reik

Sean Thomas

Pavel Zrazhevskiy

Jeff Vierstra

Michel Sadelain

Jorge Mansilla-Soto

Alexander Federation

Isabelle Riviere

Xiuyan Wang

Jocelynn Pearl

Tobias Ragoczy

Alister P W Funnell

Mingdong Liu

Alessandra Sullivan

Provided herein are methods and compositions for use in detecting on-target and/or off-target cleavage of genomic DNA in a cell by a nuclease. The on-target and off-target cleavage is detected by using oligonucleotides that bind to the single-stranded 3'-overhang created at the cleavage site. The nuclease may be an engineered nuclease comprising a nucleic acid binding domain that binds to a target nucleic acid of interest.

Compositions and methods for DNA modification detection

Disclosed herein are methods of utilizing machine learning methods to analyze microscope images of populations of cells.

Methods of analyzing microscopy images using machine learning

Provided herein are polypeptides, compositions, and methods for use thereof for genetic and epigenomic engineering, including, genome editing and gene regulation. These polypeptides and compositions include nucleic acid binding domains that bind to a target nucleic acid of interest. The nucleic acid binding domains include repeat units derived from repeat units identified in proteins from animal pathogens such as bacterium of the order Legionellales and the speciesand

Animal pathogen-derived polypeptides and uses thereof for genetic engineering

Provided herein are DNA binding domains comprising a plurality of repeat units, wherein each repeat unit is expanded or contracted in length. Also provided herein are DNA binding domains comprising a plurality of repeat units, wherein each repeat unit is separated from a neighboring repeat unit by a linker. In certain aspects, the linker includes a recognition site. Also disclosed are DNA binding proteins that include a fragment of N-cap sequence of a TALE protein. The TALE protein may be aTALE protein.

Gapped and tunable repeat units for use in genome editing and gene regulation compositions

Disclosed herein are methods for solubilizing and isolating nuclear proteins from cells.

Isolation and characterization of the nuclear proteome

Provided herein are polypeptides, compositions comprising the polypeptides and methods for genome editing and gene regulation (e.g., activation and/or repression) using the polypeptides or the compositions comprising the polypeptides, such as, DNA binding domains derived from the genus of. Also disclosed are DNA binding proteins that include a fragment of N-cap sequence of a TALE protein, such as, aTALE protein. Also disclosed are DNA binding proteins that include a fragment of N-cap sequence of a DNA binding protein derived from bacteria of the genus

Nucleic acid binding domains and methods of use thereof

Disclosed herein are methods of detecting a target nucleic acid sequence, determining the localization of the target nucleic acid sequence, and/or quantifying the number of target nucleic acid sequences in a cell. This method may be used on small target nucleic acid sequences, and may be referred to as Nano-FISH.

Methods for fluorescence imaging microscopy and nano-fish

Disclosed herein are methods of detecting a target viral nucleic acid sequence, determining the localization of the target viral nucleic acid sequence, and/or quantifying the number of target viral nucleic acid sequences in a cell. This method may be used on small target nucleic acid sequences, and may be referred to as Nano-FISH or viral Nano-FISH.

Methods and compositions for viral nano-fish

DNA cleaving enzymes are disclosed. The DNA cleaving enzymes are fused to a heterologous DNA binding domain that is designed to bind to a target nucleic acid sequence. Nucleic acids and expression cassettes encoding the DNA cleaving enzymes are also provided. Methods for genome editing using the DNA cleaving enzymes, fusion proteins, and compositions thereof are disclosed herein.

Nucleases for genome editing

Provided herein are methods for identifying high potency genomic insulator elements that can be used in a vector composition e.g., that are useful for preventing unwanted expression of neighboring genes, such as proto-oncogenes, when administered to a subject in need thereof. Also provided herein are methods for treating disease and methods for administering a nucleic acid to a subject using such vectors.

Genomic insulator elements and uses thereof

The presently disclosed subject matter provides for expression cassettes that allow for expression of a globin gene or a functional portion thereof, vectors comprising thereof, and cells transduced with such expression cassettes and vectors. The presently disclosed subject matter further provides methods for treating a hemoglobinopathy in a subject comprising administering an effective amount of such transduced cells to the subject.

Globin gene therapy for treating hemoglobinopathies

Methods for fluorescence imaging microscopy and Nano-FISH

The present disclosure is in the field of genome engineering, particularly targeted modification of the genome of a hematopoietic cell.

Growing community of inventors

Seattle, WA, United States of America

John A Stamatoyannopoulos