Massachusetts Institute of Technology

University of California

The Broad Institute, Inc.

University of Pennsylvania

The General Hospital Corporation

Boston University

Glympse Bio, Inc.

The Rockefeller University

The Salk Institute for Biological Studies

Strato/infusaid, Inc.

Sangeeta N Bhatia

Gabriel A Kwong

Andrew Warren

Tal Danino

Kelly R Stevens

Geoffrey Von Maltzahn

Michael J Sailor

Christopher S Chen

Jaideep S Dudani

Jeff Hasty

Arthur Prindle

Nathan Ross

Jing Shan

Michael T Yang

David K Wood

Ritika Chaturvedi

Jan D Baranski

Mehmet Toner

Sadik C Esener

Martin L Yarmush

Mihrimah Ozkan

Christopher J Flaim

Lev S Tsimring

Michelle Palmer

Salman R Khetani

Boyce E Collins

Sophie Cazanave

Austin Derfus

David T Eddington

Muhammad Omar Din

Sirshendu Roopom Banerjee

Vicki I Chin

Anne Carpenter Van Dyk

David Logan

Kevin Y Lin

Ester Jihae Kwon

Eric Huang

Gabriel Kwong

J Christopher Flaherty

Feng Zhang

Russell J Redmond

Darrell J Irvine

Alan Kirby Plyley

Karl Dane Wittrup

Yang Yang Li

Jun Gao

Marcela V Maus

Roderick Russell Kunz

Charles F Rice

Kenneth S Vecchio

Joshua Makower

David Benjamin Turitz Cox

Bevin Engelward

Carrolee Barlow

Giovanni Vozzi

Ester Segal

Vyas Ramanan

Liangliang Hao

Elliot E Hui

Jason Dorvee

David McDonald

Piyush K Jain

Leslie Wan-Gee Chan

Leslie W Chan

Gregory H Lambrecht

Ashish Khera

Melodi Nilgun Anahtar

Valerie Liu Tsang

Claude A Vidal

Chayanon Ngambenjawong

Arnav Chhabra

Robert Schwartz

Amir Shlomai

Jesse Kirkpatrick

Colin Buss

Ester J Kwon

Cheri Y Li

Dirk R Albrecht

Ji-Ho Park

Yin Ren

David M Weingeist

Sara Alvarez

Benjamin Migliori

Lin Chao

Rebecca Campbell

Ulla Camilla Rang

Shengyong Ng

Alice A Chen

Simone Schurle

Naveen K Mehta

Michael P Schwartz

Andrew D Warren

Disclosed herein are fusion protein, comprising (a) at least one X1 domain comprising a half-life extension compound, including but not limited to a half-life extension polypeptide; (b) at least one X2 domain comprising an anionic block; (c) at least one X3 domain comprising a linker susceptible to cleavage at a site of disease, including but not limited to a microbial infection site or tumor site; and (d) at least one X4 domain comprising a therapeutic peptide; wherein the at least one X1, X2, X3, and X4 domains are covalently linked, and each X4 domain is linked to an X3 domain without an intervening X1 or X2 domain; compositions containing such fusion proteins, and methods for their use.

Activatable therapeutic peptides and uses thereof

Immunotolerant engineered human tissue constructs are provided that are suitable for implantation into subjects. In some embodiments, the immunotolerance is controllable by an inducible system. Methods of making and using the immunotolerant engineered tissue constructs are provided.

Compositions and methods for immune tolerance

Aspects of the disclosure relate to methods and compositions useful for in vivo and/or in vitro enzyme profiling. In some embodiments, the disclosure provides methods of in vivo enzymatic processing of exogenous molecules followed by detection of signature molecules as representative of the presence of active enzymes associated with diseases or conditions. In some embodiments, the disclosure provides compositions and in vitro methods for localization of enzymatic activity in a tissue sample.

Methods to spatially profile protease activity in tissue and sections

The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also 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 to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Delivery, use and therapeutic applications of the CRISPR-Cas systems and compositions for HBV and viral diseases and disorders

Aspects of the present disclosure relate to methods and compositions useful for in vivo and/or in vitro profiling of proteases present in the lung. In some embodiments, the disclosure provides methods of in vivo enzymatic processing of exogenous molecules followed by detection of detectable markers as representative of the presence of active proteases associated with a lung disease, for example, lung cancer and lung infections. In some embodiments, the disclosure provides compositions and methods for production of a lung disease signature and diagnosis of lung disease.

Lung protease nanosensors and uses thereof

The invention relates to methods and products associated with in vivo enzyme profiling. In particular, biomarker nanoparticles capable of quantitatively detecting enzymatic activity in vivo are described. These nanoparticles can be used to detect in vivo enzyme activity. The invention also relates to products, kits, and databases for use in the methods of the invention.

Affinity-based detection of ligand-encoded synthetic biomarkers

In some aspects, the disclosure relates to compositions and method for detection, classification, and treatment of cancer. In some embodiments, the disclosure relates to protease imaging sensors comprising a scaffold linked to an enzyme-specific substrate that includes a first detectable marker capable of being released from the prostate protease sensor when exposed to an enzyme present in cancer and a tumor imaging agent comprising a second detectable marker that is linked to the scaffold. In some embodiments, the disclosure relates to methods of monitor progression of a tumor in a subject based upon detection of detectable markers in a sample obtained from a subject who has been administered a protease imaging sensor, upon detection of a tumor imaging agent, or any combination thereof.

Sensors for detecting and imaging of cancer metastasis

The present invention features assays for co-culturing primary cells while maintaining key biological activities specific to the primary cells. The invention is based, at least in part, on the discovery that compositions and methods for primary cells in a high-throughput co-culture platform, image analysis for distinguishing cells in co-cultures and assays that are suitable for screening of agents in epithelial cells, such as hepatocytes.

Systems and methods for culturing epithelial cells

A nanoparticle activity sensor containing a reporter and at least one tuning domain that modifies a distribution or residence time of the activity sensor when administered to a patient. When administered to the patient, the activity sensor enters cells or tissue where it is cleaved by enzymes specific to a physiological state such as a disease to release a detectable analyte. The tuning domains include molecular structures that modulate distribution or decay by protecting the particle from premature cleavage and indiscriminate hydrolysis, shielding the particle from immune detection and clearance, or by targeting the particle to specific tissue, bodily fluids, or cell types.

Activity sensor with tunable analyte

The present invention relates to methods and products associated with in vivo enzyme profiling. In particular, the invention relates to methods of in vivo processing of exogenous molecules followed by detection of signature molecules as representative of the presence of active enzymes associated with diseases or conditions. The invention also relates to products, kits, and databases for use in the methods of the invention.

Methods and products for in vivo enzyme profiling

The present invention provides methods of inducing proliferation of and/or differentiating cells comprising contacting cells with compounds within the methods of the invention. The present invention further provides cells obtainable by the methods of the invention.

Compounds for inducing proliferation and differentiation of cells, and methods of use thereof

The present disclosure provides patterned biomaterials having organized cords and extracellular matrix embedded in a 3D scaffold. According, the present disclosure provides compositions and applications for patterned biomaterials. Pre-patterning of these biomaterials can lead to enhanced integration of these materials into host organisms, providing a strategy for enhancing the viability of engineered tissues by promoting vascularization.

Biomaterials for enhanced implant-host integration

Some embodiments described herein relate to cells which have been genetically engineered to release a polypeptide when a population of the cells reaches a desired density. In some embodiments, the released polypeptide may be a therapeutic polypeptide. In some embodiments, the therapeutic polypeptide kills tumor cells or which inhibits the growth of tumor cells.

Engineered bacteria for production and release of therapeutics

Some aspects of this invention provide reagents and methods for the sensitive, quantitative and simultaneous detection of target analytes in complex biological samples by liquid chromatography tandem mass spectrometry (LC MS/MS). Some aspects of this invention provide affinity reagents encoded with mass reporters for the sensitive and quantitative translation of an analyte of interest into a mass tag. The reagents and methods provided herein have general utility in analyte detection and encoding, for example, in biomolecular profiling, molecular diagnostics, and biochemical encoding.

Multiplexed detection with isotope-coded reporters

Growing community of inventors

Lexington, MA, United States of America

Sangeeta N Bhatia