Massachusetts Institute of Technology

The Broad Institute, Inc.

Harvard College

Children's Medical Center Corporation

The Rockefeller University

Neville Espi Sanjana

Feng Zhang

Ophir Shalem

Bernd Zetsche

Winston X Yan

Phillip A Sharp

Patrick D Hsu

Le Cong

Stuart H Orkin

Daniel E Bauer

Randall Jeffrey Platt

David Root

John G Doench

Sara Jones

Ella Nicole Biewener Hartenian

David Bikard

Fei Ran

Luciano Marraffini

David Benjamin Turitz Cox

Mark Daniel Brigham

Sidi Chen

Jason Wright

Wenyan Jiang

David Olivier Bikard

Silvana Konermann

Shauiliang Lin

The present invention generally relates to compositions, methods applications and screens used in functional genomics that focus on gene function in a cell and that may use vector systems and other aspects related to Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas systems and components thereof. 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 and methods for utilizing the CRISPR-Cas system.

Functional genomics using CRISPR-Cas systems, compositions, methods, knock out libraries and applications thereof

The present invention generally relates to libraries, compositions, methods, applications, kits and screens used in functional genomics that focus on gene function in a cell and that may use vector systems and other aspects related to Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas systems and components thereof. 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 and methods for utilizing the CRISPR-Cas system.

Functional genomics using CRISPR-Cas systems, compositions, methods, screens and applications thereof

The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.

CPF1 complexes with reduced indel activity

The present invention relates to in vivo methods for modeling tumor formation and/or tumor evolution comprising the use of eukaryotic cells in which one or more genetic target locus has been altered by the CRISPR/Cas system, and which cells are transplanted in non-human eukaryote as a model system for tumor formation and tumor evolution. In particular in vivo genetic screening methods for identifying genes involved in tumorigenesis and metastasis are disclosed. The invention further relates to kits and components for practicing the methods, as well as materials obtainable by the methods, in particular tumor and metastasis samples and cells or cell lines derived therefrom. The invention also relates to diagnostic and therapeutic methods derived from the information obtained in the modeling methods.

CRISPR mediated in vivo modeling and genetic screening of tumor growth and metastasis

The application relates to a deep scanning mutagenesis library to interrogate phenotypic changes in a population of cells comprising a plurality of CRISPR-Cas system guide RNAs targeting genomic sequences within at least one continuous genomic region, wherein the guide RNAs target at least 100 genomic sequences upstream of a PAM sequence for every 1000 base pairs within the continuous genomic region and methods for their use.

Functional genomics using CRISPR-Cas systems for saturating mutagenesis of non-coding elements, compositions, methods, libraries and applications thereof

Provided herein are nucleic acid molecules that target the BCL11A enhancer functional regions, compositions comprising the nucleic acid molecules and methods for increasing fetal hemoglobin levels in a cell by disrupting BCL11A expression at the genomic level. Also provided herein are methods and compositions relating to the treatment of hemoglobinopathies by reinduction of fetal hemoglobin levels. In particular, the nucleic acid molecules target the +62, +58, and/or the +55 enhancer functional regions.

Targeting BCL11A enhancer functional regions for fetal hemoglobin reinduction

Cpf1 complexes with reduced indel activity

The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. 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 and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system.

CRISPR-Cas component systems, methods and compositions for sequence manipulation

The invention provides for engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. 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 with additional functional domains. Also provided are methods of directing CRISPR complex formation in prokaryotic and eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity.

Engineering and optimization of systems, methods and compositions for sequence manipulation with functional domains

Growing community of inventors

Cambridge, MA, United States of America

Neville Espi Sanjana