The University of Tokyo

Massachusetts Institute of Technology

The Broad Institute, Inc.

Harvard College

Shionogi Company Limited

Tohoku University

Modalis Therapeutics Corporation

Hiroshi Nishimasu

Osamu Nureki

Feng Zhang

Ryuichiro Ishitani

Fei Ran

Hisato Hirano

Patrick D Hsu

Silvana Konermann

Mark Daniel Brigham

Tetsuo Nagano

Le Cong

Winston X Yan

Nobuyuki Tanaka

Hirotatsu Kojima

Takayoshi Okabe

Chie-yu Lin

Yinqing Li

Yusuke Tateno

Tetsuya Yamagata

Yuanbo Qin

Iain Robert Thompson

Junken Aoki

Mitsuyasu Kawaguchi

Junji Yamane

Alexandro Trevino

Shohei Kajimoto

Keith M Connolly

Manabu Katou

Shiro Kida

Yasuhiko Kanda

Chiaki Fujikoshi

Chie-Yu Lin

Kaijie Zheng

Masahide Odan

Yoshiyuki Kioi

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.

Systems, methods and compositions for sequence manipulation with optimized functional CRISPR-Cas systems

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

A mutant SaCas9 protein such as a protein having an amino acid sequence resulting from mutations of glutamic acid at the 782-position to lysine (E782K), leucine at the 800-position to arginine (L800R), asparagine at the 968-position to arginine (N968R), asparagine at the 985-position to alanine (N985A), arginine at the 991-position to alanine (R991A), alanine at the 1021-position to serine (A1021S), threonine at the 927-position to lysine (T927K), lysine at the 929-position to asparagine (K929N), and isoleucine at the 1017-position to phenylalanine (I1017F) in SEQ ID NO: 2 has relaxed restriction on target sequence while maintaining binding ability to guide RNA, and is useful as a tool for gene editing.

Modified CAS9 protein, and use thereof

The present invention aims to provide a modified Cas9 protein with relaxed restriction on target sequence while maintaining binding ability to guide RNA, and use thereof. A protein containing the amino acid sequence of SEQ ID NO: 1 in which the 1335-position arginine is mutated into alanine (R1335A), isoleucine (R1335I), methionine (R1335M), threonine (R1335T) or valine (R1335V), the 1111-position leucine is mutated into arginine (L1111R), the 1135-position aspartic acid is mutated into valine (D1135V), the 1218-position glycine is mutated into arginine (G1218R), the 1219-position glutamic acid is mutated into phenylalanine (E1219F), the 1322-position alanine is mutated into arginine (A1322R), and the 1337-position threonine is mutated into arginine (T1337R), and the like.

Polynucleotide encoding modified CAS9 protein

Modified Cas9 protein and use thereof

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.

CRISPR-Cas systems, crystal structure and uses thereof

The present invention provides a compound of formula (1), wherein R, R, R, R, R, Rand Rare as defined in the description, which has an autotaxin inhibitory activity, a pharmaceutical composition comprising the compound as an active ingredient, and a method of prevention or treatment of a disease involving autotaxin, which is characterized by administering the compound. 

Fused pyrazole derivative having autotaxin inhibitory activity

A compound according to any one of formula (Ia) to (Ic), or its pharmaceutically acceptable salt: 

Pyrimidinone derivative having autotaxin-inhibitory activity

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Tokyo, Japan

Hiroshi Nishimasu