The Broad Institute, Inc.

Massachusetts Institute of Technology

Harvard College

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

Rutgers, the State University of New Jersey

Whitehead Institute for Biomedical Research

Skolkovo Institute of Science and Technology

Baylor College of Medicine

Abudayyeh, Omar O.

Joung, Julia

Minakhin, Leonid

Makarova, Kira S.

Severinov, Konstantin

Semenova, Ekaterina

Lander, Eric S.

Eric S Lander

Feng Zhang

Omar O Abudayyeh

Jonathan S Gootenberg

James Joseph Collins

Aviv Regev

Silvana Konermann

Le Cong

Erez Lieberman Aiden

Andreas Gnirke

Pardis Sabeti

David Benjamin Turitz Cox

Mitchell Guttman

Konstantin Severinov

Brian Cleary

Alexandre Melnikov

Eugene Koonin

Tarjei Mikkelsen

Aaron Smargon

Sergey Shmakov

Kira S Makarova

Yuri I Wolf

David Altshuler

Ekaterina Semenova

Cameron Myhrvold

Elena Stamenova

Neena Pyzocha

Julia Joung

Catherine Amanda Freije

Omar Abudayyeh

Leonid Minakhin

Su-Chen Huang

Li Wang

Xiaolan Zhang

Suhas SP Rao

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.

Crispr enzymes and systems

Provided herein is a nucleic acid detection system comprising: a CRISPR system comprising an effector protein and one or more guide RNAs designed to bind to corresponding target molecules; an RNA-based masking construct; and optionally, nucleic acid amplification reagents to amplify target RNA molecules in a sample. In another aspect, the embodiments provide a polypeptide detection system comprising: a CRISPR system comprising an effector protein and one or more guide RNAs designed to bind a trigger RNA, an RNA-based masking construct; and one or more detection aptamers comprising a masked RNA polymerase promoter binding site or a masked primer binding site. In some embodiments, the system may be used to detect viruses in samples.

CRISPR effector system based diagnostics for virus detection

The present invention relates to tissue and cell imaging utilizing genomic informatics and gene-expression profiling. Gene-expression profiles utilized in methods to obtain in situ imaging of cells and tissues provide complex molecular fingerprints regarding the relative state of a cell or tissue.

Compressed sensing for screening and tissue imaging

The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect broth DNA and RNA with comparable levels of sensitivity and can differentiate targets from non-targets based on single base pair differences. Moreover, the embodiments disclosed herein can be prepared in freeze-dried format for convenient distribution and point-of-care (POC) applications. Such embodiments are useful in multiple scenarios in human health including, for example, viral detection, bacterial strain typing, sensitive genotyping, and detection of disease-associated cell free DNA.

CRISPR effector system based diagnostics

The present invention relates to genomic informatics and gene-expression profiling. Gene-expression profiles provide complex molecular fingerprints regarding the relative state of a cell or tissue. Similarities in gene-expression profiles between organic states provide molecular taxonomies, classification, and diagnostics. Similarities in gene-expression profiles resulting from various external perturbations reveal functional similarities between these perturbagens, of value in pathway and mechanism-of-action elucidation. Similarities in gene-expression profiles between organic and induced states may identify clinically-effective therapies. Systems and methods herein provide for the measurement of relative gene abundances, including unbiased selection of and construction of probes and targets designed and methods for using known properties of sparsity of measurements to reach gene abundances.

Systems and methods for determining relative abundances of biomolecules

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.

Type VI CRISPR orthologs and systems

The invention provides methods for determining the activity of a plurality of nucleic acid regulatory elements. These methods may facilitate, e.g., the systematic reverse engineering, and optimization of mammalian cis-regulatory elements at high resolution and at a large scale. The method may include integration of multiplexed DNA synthesis and sequencing technologies to generate and quantify the transcriptional regulatory activity of e.g., thousands of arbitrary DNA sequences in parallel in cell-based as says (e.g., mammalian cell based assays).

Multiplexed genetic reporter assays and compositions

The present invention provides a computer method and apparatus for detecting mutations in DNA fragments. Specifically, percent acetonitrile and threshold temperature, for use in the denaturing high performance liquid chromatography method of separating DNA fragments, are determined. In a preferred embodiment, the present invention serves as a preprocessor to the DHPLC system described in the cited art.

Computer method and apparatus for analyzing mutations in DNA

Growing community of inventors

Cambridge, MA, United States of America

Eric S Lander