The United States of America, as Represented by the Secretary, Department of Health and Human Services

Massachusetts Institute of Technology

Rutgers, the State University of New Jersey

The Broad Institute, Inc.

Harvard College

Skolkovo Institute of Science and Technology

California Institute of Technology

Abudayyeh, Omar O.

Joung, Julia

Minakhin, Leonid

Makarova, Kira S.

Severinov, Konstantin

Semenova, Ekaterina

Lander, Eric S.

Shmakov, Sergey

Eugene Koonin

Feng Zhang

Kira S Makarova

Yuri I Wolf

Sergey Shmakov

Omar O Abudayyeh

Jonathan S Gootenberg

Silvana Konermann

Konstantin Severinov

Julia Joung

Ekaterina Semenova

Leonid Minakhin

Eric Lander

David Arthur Scott

Winston X Yan

Raymond J Deshaies

Eric S Lander

Aaron Smargon

Rati Verma

Neena Pyzocha

Gregory Cope

Xavier Ambroggio

David Cox

Lakshminarayanan Aravind

Disclosed here is a method of identifying novel CRISPR effectors, comprising: identifying sequences in a genomic or metagenomic database encoding a CRISPR array; identifying one or more Open Reading Frames (ORFs) in said selected sequences within 10 kb of the CRISPR array; discarding all loci encoding proteins which are assigned to known CRISPR-Cas subtypes and, optionally, all loci encoding a protein of less than 700 amino acids; and identifying putative novel CRISPR effectors, and optionally classifying them based on structure analysis.

Methods for identifying class 2 crispr-cas systems

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

Crispr enzymes and systems

CRISPR enzymes and systems

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

The present invention is based on the discovery that a polypeptide containing the JAB subunit or the JAM domain has peptidase activity, e.g., isopeptidase activity. The present invention provides polypeptides and crystalline polypeptides containing the JAM domain and methods of using such polypeptides to screen for agents capable of affecting the peptidase activity of the polypeptides. The present invention also provides methods of using the JAM domain for rational drug design or identifying agents capable of affecting the peptidase activity of the JAM domain.

Regulation of target protein activity through modifier proteins

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Bethesda, MD, United States of America

Eugene Koonin