Massachusetts Institute of Technology

The Broad Institute, Inc.

Harvard College

Leland Stanford Junior University

University of Iowa Research Foundation

The University of Tokyo

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

Rutgers, the State University of New Jersey

Children's Medical Center Corporation

The Rockefeller University

The General Hospital Corporation

University of Pittsburgh

Dana-Farber-Cancer Institute Inc.

Tufts University

Massachusetts Eye and Ear Infirmary

Feng Zhang

Omar O Abudayyeh

Jonathan S Gootenberg

Viviana Gradinaru

Bernd Zetsche

Le Cong

Fei Ran

Ian Slaymaker

Neville Espi Sanjana

Eric Lander

David Benjamin Turitz Cox

Edgardo Rodriguez

Edward Stuart Boyden

George M Church

Daniel Griffith Anderson

Karl A Deisseroth

Silvana Konermann

Patrick D Hsu

James Joseph Collins

David Arthur Scott

Winston X Yan

Beverly L Davidson

Randall Jeffrey Platt

M Bret Schneider

Osamu Nureki

Hiroshi Nishimasu

Han Altae-Tran

Julia Joung

Chie-yu Lin

Aviv Regev

Eric S Lander

Alim Ladha

Mark Daniel Brigham

Linyi Gao

Ophir Shalem

Eugene Koonin

Aaron Smargon

Yuri I Wolf

Sergey Shmakov

Kira S Makarova

Matthias Heidenreich

Jordi Mata-Fink

Alexis Borisy

James E Dahlman

Deborah Palestrant

Konstantin Severinov

Ryuichiro Ishitani

Yinqing Li

Guilhem Faure

Ekaterina Semenova

Lukasz Swiech

Neena Pyzocha

Leonid Minakhin

Chie-Yu Lin

Soumya Kannan

Sourav Choudhury

Joshua Asher Weinstein

Phillip A Sharp

Jaimie M Henderson

Stuart H Orkin

Pardis Sabeti

Daniel E Bauer

Sriram Kosuri

Cameron Myhrvold

Sidi Chen

David Root

Guoping Feng

John G Doench

Catherine Amanda Freije

Jason Wright

Jonathan Strecker

Sara Jones

Alexandro Trevino

Alexander Aravanis

Johnathan S Gootenberg

Ella Nicole Biewener Hartenian

Yang Zhou

Sangeeta N Bhatia

Henry Ignatius Smith

David Jacob Mishelevich

David A Weitz

Paul Blainey

David Bikard

Charles F Rice

Luciano Marraffini

Levi A Garraway

Deborah Hung

Amit Choudhary

Jennifer Rubin Grandis

James Gregory Goodberlet

Jeffrey Todd Hastings

David Feldman

Anindita Basu

Roby Bhattacharyya

Jesse Engreitz

Vyas Ramanan

Omar Abudayyeh

David Cox

Naomi Habib

Systems and methods for rapid diagnostics related to the use of CRISPR effector systems and optimized guide sequences for detection of coronavirus, including multiplex lateral flow diagnostic devices and methods of use, are provided.

Crispr effector system based coronavirus diagnostics

FUNCTIONAL GENOMICS USING CRISPR-CAS SYSTEMS FOR SATURATING MUTAGENESIS OF NON-CODING ELEMENTS, COMPOSITIONS, METHODS, LIBRARIES AND APPLICATIONS THEREOF

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 disclosure includes non-naturally occurring or engineered CRISPR Cas9, each associated with at least one destabilization domain (DD), along with compositions, systems and complexes involving the DD-CRISPR Cas9, nucleic acid molecules and vectors encoding the same, delivery systems involving the same, uses therefor.

CRISPR having or associated with destabilization domains

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 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 to be used in optimized CRISPR-Cas enzyme systems.

Engineering of systems, methods and optimized guide compositions with new architectures for sequence manipulation

Embodiments of the disclosure include compositions and methods for treating diseases (e.g., brain diseases) using genetic engineered cells. In some cases, the cells are engineered hematopoietic stem cells (HSCs), which are capable of engrafting to a central nervous system and differentiating to progeny cells (e.g., microglial cells).

Microglial progenitors for regeneration of functional microglia in the central nervous system and therapeutics uses thereof

The present invention offers a new approach for highly multiplexed, programmable antiviral therapies that directly target viral RNA, and can be flexibly adapted to target novel viruses or emerging outbreak pathogens. Class 2, type VI CRISPR system-based therapies can be used in combination with existing antiviral compounds for viruses where such compounds exist, either by increasing their efficacy or by preventing the evolution of specific drug resistance mutations. Perhaps most excitingly, if a virus evolves resistance to a specific guide RNA sequence, it is easy to switch to a different guide RNA sequence, or to design a new guide sequence to target the new mutation. Such approaches should prevent the widespread development of resistance to Class 2, type VI CRISPR system-based therapies.

CRISPR system based antiviral therapy

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. Methods for making and using and uses of such systems, methods, and compositions and products from such methods and uses are also disclosed and claimed.

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-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA. Aspects of the invention in particular relate to Cpf1 mutants having altered PAM specificity.

CRISPR enzymes and systems with modified pam specificity

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

Compositions and methods of use of CRISPR-Cas systems in nucleotide repeat disorders

The present invention generally relates to plants comprising a CRISPR system or parts of a CRISPR system, compositions, containers, polynucleotide, vectors, delivery systems, parts of plants, methods for production, CRISPR systems, and components thereof. Further aspects of the invention include a method for identifying a CRISPR system which is functional in a plant cell and a method for improving a CRISPR system in a plant.

CRISPR-systems for modifying a trait of interest in a plant

The disclosure includes non-naturally occurring or engineered CRISPR systems and proteins, associated with a delivery system comprising a virus component and a lipid component. The disclosure includes CRISPR proteins associated with capsid proteins, e.g., AAV VP1VP2, and/or VP3, on the surface of or internal to the AAV, along with compositions, systems and complexes involving the AAV-CRISPR protein, nucleic acid molecules and vectors encoding the same, deliver}-systems, and uses therefor.

Delivery of large payloads

Growing community of inventors

Cambridge, MA, United States of America

Feng Zhang