Massachusetts Institute of Technology

The Broad Institute, Inc.

Harvard College

The Rockefeller University

Randall Jeffrey Platt

Feng Zhang

Daniel Griffith Anderson

Guoping Feng

Yang Zhou

Phillip A Sharp

Patrick D Hsu

Le Cong

Ian Slaymaker

Fei Ran

Luciano Marraffini

James E Dahlman

Neville Espi Sanjana

David Benjamin Turitz Cox

Matthias Heidenreich

Sidi Chen

Lukasz Swiech

Wenyan Jiang

David Olivier Bikard

Shauiliang Lin

Robert Langer

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, Engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications

Methods and compositions for inducing a plurality of mutations in transgenic Cas9 eukaryotes to model a neuronal disease or disorder. The invention further comprehends testing putative treatments with such models, e.g., testing putative chemical compounds that may be pharmaceutically relevant for treatment or gene therapy that may be relevant for treatment, or combinations thereof. The invention allows for the study of genetic diseases and putative treatments to better understand and alleviate a genetic disease or a condition, e.g., autism, autism-spectrum disease or disorder, obsessive-compulsive disorder, or psychiatric disorders.

Use and production of CHD8+/&#x2212; transgenic animals with behavioral phenotypes characteristic of autism spectrum disorder

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 invention involves inducing 3-50 or more mutations (e.g., any whole number between 3 and 50 of mutations, with it noted that in some embodiments there can be up to 16 different RNA(s), e.g., sgRNAs each having its own a promoter, in a vector, such as AAV, and that when each sgRNA does not have its own promoter, there can be twice to thrice that amount of different RNA(s), e.g., sgRNAs, e.g., 32 or even 48 different guides delivered by one vector) in transgenic Cas9 eukaryotes to model genetic disease, e.g. cancer. The invention comprehends testing putative treatments with such models, e.g., testing putative chemical compounds that may be pharmaceutically relevant for treatment or gene therapy that may be relevant for treatment, or combinations thereof. The invention allows for the study of genetic diseases and putative treatments to better understand and alleviate a genetic disease or a condition, e.g., cancer.

Delivery, use and therapeutic applications of the CRISPR-Cas systems and compositions for modeling competition of multiple cancer mutations in vivo

Delivery, engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications

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

Randall Jeffrey Platt