Massachusetts Institute of Technology

The Broad Institute, Inc.

Harvard College

The Brigham and Women's Hospital, Inc.

The University of Tokyo

University of California

University of Pittsburgh

Dana-farber-cancer Institute Inc.

Massachusetts Eye and Ear Infirmary

Instituto Carlos Slim De La Salud, A.c.

President and Fellows of Havard College

The Rockefeller University

Le Cong

Feng Zhang

Fei Ran

Aviv Regev

Randall Jeffrey Platt

George M Church

Eric Lander

Vijay K Kuchroo

Winston X Yan

Chao Wang

Ana Carrizosa Anderson

Osamu Nureki

Hiroshi Nishimasu

Neville Espi Sanjana

Meromit Singer

Matthias Heidenreich

Brian Cleary

Silvana Konermann

Patrick D Hsu

Alexander K Shalek

Luciano Marraffini

Sriram Kosuri

Yinqing Li

Lukasz Swiech

Levi A Garraway

Orit Rozenblatt-Rosen

Jennifer Rubin Grandis

David Benjamin Turitz Cox

Eric S Lander

Jonathan S Weissman

Mark Daniel Brigham

Jellert Gaublomme

Thomas W Norman

Atray Dixit

Oren Parnas

Naomi Habib

Wenyan Jiang

Brittany Adamson

Ann Marie Egloff

Nicholas Stransky

Aaron D Tward

Kaijie Zheng

Sam Locascio

David Olivier Bikard

Shauiliang Lin

The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems. In particular the present invention comprehends engineered new guide architectures and enzymes to be used in optimizedCRISPR-Cas enzyme systems.

Engineering and optimization of systems, methods, enzymes and guide scaffolds of CAS9 orthologs and variants for sequence manipulation

The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues of organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provide dare methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Delivery and use of the CRISPR-CAS systems, vectors and compositions for hepatic targeting and therapy

The present invention relates to genomic informatics and gene-expression profiling. Gene-expression profiles provide complex molecular fingerprints regarding the relative state of a cell or tissue. Similarities in gene-expression profiles between organic states provide molecular taxonomies, classification, and diagnostics. Similarities in gene-expression profiles resulting from various external perturbations reveal functional similarities between these perturbagens, of value in pathway and mechanism-of-action elucidation. Similarities in gene-expression profiles between organic and induced states may identify clinically-effective therapies. Systems and methods herein provide for the measurement of relative gene abundances, including unbiased selection of and construction of probes and targets designed and methods for using known properties of sparsity of measurements to reach gene abundances.

Systems and methods for determining relative abundances of biomolecules

Provided herein are compositions, kits and methods useful in the construction of designer transcription activator-like effector (dTALE) polypeptides.

Transcription activator-like effectors

The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Delivery, use and therapeutic applications of the CRISPR-Cas systems and compositions for genome editing

The present invention generally relates to methods and compositions used delivery of gene editing compositions including transcriptional effectors with parvovirus and preferred methods for making same.

Recombinant virus and preparations thereof

The invention relates to methods of altering expression of a genomic locus of interest or specifically targeting a genomic locus of interest in an animal cell, which may involve contacting the genomic locus with a non-naturally occurring or engineered composition that includes a deoxyribonucleic acid (DNA) binding polypeptide having a N-terminal capping region, a DNA binding domain comprising at least five or more Transcription activator-like effector (TALE) monomers and at least one or more half-monomers specifically ordered to target the genomic locus of interest, and a C-terminal capping region, wherein the polypeptide includes at least one or more effector domains, and wherein the polypeptide is encoded by and translated from a codon optimized nucleic acid molecule so that the polypeptide preferentially binds to the DNA of the genomic locus.

Nucleotide-specific recognition sequences for designer TAL effectors

The present invention provides tools and methods for the systematic analysis of genetic interactions, including higher order interactions. The present invention provides tools and methods for combinatorial probing of cellular circuits, for dissecting cellular circuitry, for delineating molecular pathways, and/or for identifying relevant targets for therapeutics development.

Assays for massively combinatorial perturbation profiling and cellular circuit reconstruction

The present invention provides markers, marker signatures and molecular targets that correlate with dysfunction of immune cells and are advantageously independent of the immune cell activation status. The present markers, marker signatures and molecular targets provide for new ways to evaluate and modulate immune responses. Specifically, POU2AF1 modulation is provided for use as a marker, marker signature and molecular target. Therapeutic methods are also provided to treat a patient in need thereof who would benefit from an increased immune response.

Compositions and methods for evaluating and modulating immune responses by detecting and targeting POU2AF1

The present invention provides markers, marker signatures and molecular targets that correlate with dysfunction of immune cells and are advantageously independent of the immune cell activation status. The present markers, marker signatures and molecular targets provide for new ways to evaluate and modulate immune responses. Specifically, GATA3 and/or FOXO1 modulation are provided for use as markers, marker signatures and molecular targets. Therapeutic methods are also provided to treat a patient in need thereof who would benefit from an increased immune response.

Compositions and methods for evaluating and modulating immune responses by detecting and targeting GATA3

Delivery, use and therapeutic applications of the CRISPR-Cas systems and compositions for targeting disorders and diseases using viral components

Delivery and use of the CRISPR-Cas systems, vectors and compositions for hepatic targeting and therapy

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Cambridge, MA, United States of America

Le Cong