Boston University

Massachusetts Institute of Technology

Harvard College

The Broad Institute, Inc.

The General Hospital Corporation

Arizona State University

Cellicon Technologies, Inc.

Other

Afferent Corporation

James Joseph Collins

Timothy Kuan-Ta Lu

Feng Zhang

Omar O Abudayyeh

Jonathan S Gootenberg

Eric Lander

Alexander A Green

Stephen J Kleshinski

Jason D Harry

James B Niemi

Timothy S Gardner

Peng Yin

Douglas Ewen Cameron

Kyle R Allison

Mark P Brynildsen

Daniel J Dwyer

Russell-John Krom

Charles Cantor

Robert James Citorik

Eric S Lander

Keith Pardee

Farren J Isaacs

Jongmin Kim

Guillaume Lambert

Thomas Ferrante

Dana Braff

Attila A Priplata

Melissa K Takahashi

Michael Andrew Lobritz

Dirk Ahlgrim

Gregory N Stephanopoulos

Aviv Regev

Arun Dhyaneshwar Chawan

Ron Weiss

Robert J Wood

Hideki Kobayashi

Michael Thormann

Andreas Treml

Ari E Friedland

Deborah Hung

Michael Almstetter

Pardis Sabeti

Kollol Pal

Samuel Moskowitz

Michael Sandor Koeris

Roby Bhattacharyya

Hani Sallum

Ahmad S Khalil

Timothy Lu

Cameron Myhrvold

James Niemi

Gregg Draudt

Arnaud Gutierrez

Catherine Amanda Freije

Omar Abudayyeh

Catherine Spina

Prerna Saluja Bhargava

Ning Mao

Daniel Neafsey

J Timothy Inglis

Jeong Wook Lee

Angela Early

Carlo J De Luca

David J Christini

Sylvain Meylan

Tanguy My Chau

Caleb J Bashor

Christopher Jongsoo Yoon

Elvira Vitu

Casper Enghuus

Jeremy Jonathan Gam

Nikit Patel

J Ruben Morones-Ramirez

Jonathan Alexander Winkler

Tara L Deans

Guillaume Cottarel

Jamey Wierzbowski

Michael Kohanski

Atilla A Priplata

Boris Hayete

Jeremiah Faith

Mads Kearn

Michihiro Araki

Tsz Yan Clement Chan

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 disclosure is related to an engineered nucleic acid encoding a post-poly A signal RNA 3' to a terminator for expression of protein, and/or non-coding RNA. Also provided herein are methods for reducing epigenetic silencing, genetic modification, transcriptional regulation of the engineered nucleic acid described herein.

Engineered post-poly A signal RNA and uses thereof

Methods for detecting the presence of a pathogen infection are described. In particular, this document provides a method of detecting target nucleic acids, such as pathogen-specific RNA, in a biological sample obtained from a subject, where the method comprises using one or more toehold switch sensors and an isothermal amplification step to detect the target nucleic acid. Methods specific for detecting and identify the presence of a virus such as Zika virus are also provided.

Portable, low-cost pathogen detection and strain identification platform

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 invention provides novel and versatile classes of riboregulators, including inter alia activating and repressing riboregulators, switches, and trigger and sink RNA, and methods of their use for detecting RNAs in a sample such as a well and in modulating protein synthesis and expression.

Compositions comprising riboregulators and methods of use thereof

Embodiments disclosed herein provide artificial expression systems comprising multivalent transcription factor complexes for cooperative transcription factor assembly and modulating gene expression. More specifically, engineered synthetic transcription factors are recruited and structurally organized on synthetic gene circuits using molecular clamps, where the strength of intra-complex interactions can be modulated for fine tuning of gene expression as desired.

Systems and methods for control of gene expression

CRISPR effector system based diagnostics for malaria detection

Provided herein, in some embodiments, are engineered phagemids that comprise at least one synthetic genetic circuit, wherein the at least one synthetic genetic circuit comprises gene sequences encoding at least one non-lytic antimicrobial peptides (AMPs) and/or antibacterial toxin proteins, a stable origin of replication, and a bacteriophage-packaging signal, wherein the engineered phagemid does not comprise some or all gene sequences encoding bacteriophage proteins required for assembly of a bacteriophage particle.

Engineered phagemids

Provided herein are systems, methods and compositions for rendering cells or the expression of an effector protein sensitive to a predetermined condition. In one aspect, cells can be rendered dependent upon the presence of an environmental agent, e.g., an exogenous agent, without which the cell will default to expression of a death protein and be killed. In another aspect, cells can be rendered sensitive to the presence of a set of predetermined conditions such that cells will only grow when two or more necessary exogenous agents are supplied, and without either of which, the cells are killed. In this aspect, hybrid transcription factors provide a vast array of possible predetermined conditions.

Deadman and passcode microbial kill switches

Provided herein are compositions and methods to improve treatment of chronic infections, and reduce, delay, or inhibit formation of biofilms, using specific combinations of aminoglycoside antibiotics and treatment with one or more proton motive force (PMF) stimulating compounds. These novel methods are easily adapted to clinical settings as toxicity and efficacy of the antibiotics and metabolites used have already been studied in vivo, and as dosing for both the antibiotics and metabolites are known.

Intermediate metabolism products to potentiate aminoglycoside antibiotics in bacterial infections

The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect both 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.

A method and wearable system and for enhancing human balance and gait and preventing foot injury through neurological stimulation of the foot and the ankle. Subthreshold stimulation for neurosensory enhancement is provided via electrodes or vibrational actuators, or combination thereof, disposed in or on a wearable a platform, such as an insole, sock shoe, removable shoe insert, or applied without the support of a platform, to the skin surface of an individual. Suprathreshold stimulation for therapeutic purposes, such as improving blood flow, is also provided by the vibrational actuators. The actuators and electrodes are driven by bias signals generated by a bias signal generator that is coupled to a controller. The signal generator under the control of the controller is adapted to generate a non-deterministic random signal, a repetitive pattern or series of patterns. The controller optionally includes a communication port for interfacing with an external computer for purposes of optimizing and programming the controller. The wearable system is powered by a power source.

Method and apparatus for improving human balance and gait and preventing foot injury

Growing community of inventors

Newton, MA, United States of America

James Joseph Collins